Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
November-2021 Volume 22 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2021 Volume 22 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review)

  • Authors:
    • Lin-Rui Ma
    • Jia-Xin Li
    • Ling Tang
    • Run-Ze Li
    • Jia-Shun Yang
    • Ao Sun
    • Elaine Lai‑Han Leung
    • Pei-Yu Yan
  • View Affiliations / Copyright

    Affiliations: Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, P.R. China, Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Rehabilitation Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 787
    |
    Published online on: September 14, 2021
       https://doi.org/10.3892/ol.2021.13048
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Lung cancer is the most common type of cancer with the highest mortality rate worldwide. Non‑small cell lung cancer (NSCLC) accounts for ~85% of the total number of lung cancer cases. In the past two decades, immunotherapy has become a more promising treatment method than traditional treatments (surgery, radiotherapy and chemotherapy). Immunotherapy has been shown to improve the survival rate of patients and to have a superior effect when controlling lung cancer than traditional therapy. However, only a small number of patients can benefit from immunotherapy, and not all patients who qualify experience long‑term benefits. In the clinic, the objective response rate of programmed cell death protein 1 treatment without the prior screening of patients is only 15‑20%. Immunotherapy is associated with both opportunities and challenges for patients with NSCLC. The current challenges of immunotherapy include the lack of accurate biomarkers, inevitable resistance and insufficient understanding of immune checkpoints. In previous years, several methods for overcoming the challenges posed by immunotherapy have been proposed, but combination therapy is the most suitable choice. A large number of studies have shown that the combination of drugs can significantly improve their efficacy, compared with monotherapy, and that some therapeutic combinations have been approved by the Food and Drug Administration for the treatment of NSCLC. Traditional Chinese medicine (TCM) is a traditional medical practice in China that can play an important role in immunotherapy. Most agents used in TCM originate from plants, and have the advantages of low toxicity and multiple targets. In addition, TCM includes a unique class of drugs that can improve autoimmunity. Therefore, TCM may be a promising treatment method for all types of cancer.
View Figures

Figure 1

View References

1 

Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A and Bray F: Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 144:1941–1953. 2019. View Article : Google Scholar : PubMed/NCBI

2 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Gridelli C, Rossi A, Carbone DP, Guarize J, Karachaliou N, Mok T, Petrella F, Spaggiari L and Rosell R: Non-small-cell lung cancer. Nat Rev Dis Primers. 1:150092015. View Article : Google Scholar : PubMed/NCBI

4 

Zheng YW, Li RM, Zhang XW and Ren XB: Current adoptive immunotherapy in non-small cell lung cancer and potential influence of therapy outcome. Cancer Invest. 31:197–205. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Herbst RS, Morgensztern D and Boshoff C: The biology and management of non-small cell lung cancer. Nature. 553:446–454. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Bagchi S, Yuan R and Engleman EG: Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance. Annu Rev Pathol. 16:223–249. 2021. View Article : Google Scholar : PubMed/NCBI

7 

Somasundaram A and Burns TF: The next generation of immunotherapy: Keeping lung cancer in check. J Hematol Oncol. 10:872017. View Article : Google Scholar : PubMed/NCBI

8 

Shi T, Ma Y, Yu L, Jiang J, Shen S, Hou Y and Wang T: Cancer immunotherapy: A focus on the regulation of immune checkpoints. Int J Mol Sci. 19:13892018. View Article : Google Scholar : PubMed/NCBI

9 

Joller N and Kuchroo VK: Tim-3, Lag-3, and TIGIT. Curr Top Microbiol Immunol. 410:127–156. 2017.PubMed/NCBI

10 

Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA and Sharpe AH: Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 3:541–547. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Leach DR, Krummel MF and Allison JP: Enhancement of antitumor immunity by CTLA-4 blockade. Science. 271:1734–1736. 1996. View Article : Google Scholar : PubMed/NCBI

12 

Ostrov DA, Shi W, Schwartz JC, Almo SC and Nathenson SG: Structure of murine CTLA-4 and its role in modulating T cell responsiveness. Science. 290:816–819. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Iida T, Ohno H, Nakaseko C, Sakuma M, Takeda-Ezaki M, Arase H, Kominami E, Fujisawa T and Saito T: Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells. J Immunol. 165:5062–5068. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Sharpe AH and Freeman GJ: The B7-CD28 superfamily. Nat Rev Immunol. 2:116–126. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Buchbinder EI and Desai A: CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. Am J Clin Oncol. 39:98–106. 2016. View Article : Google Scholar : PubMed/NCBI

16 

de Miguel M and Calvo E: Clinical challenges of immune checkpoint inhibitors. Cancer Cell. 38:326–333. 2020. View Article : Google Scholar : PubMed/NCBI

17 

Ishida Y, Agata Y, Shibahara K and Honjo T: Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11:3887–3895. 1992. View Article : Google Scholar : PubMed/NCBI

18 

Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, Shin T, Tsuchiya H, Pardoll DM, Okumura K, et al: Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 169:5538–5545. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Patel SP and Kurzrock R: PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 14:847–856. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M and Saito T: Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 209:1201–1217. 2012. View Article : Google Scholar : PubMed/NCBI

21 

O'Kane GM, Labbé C, Doherty MK, Young K, Albaba H and Leighl NB: Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 22:70–80. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Wang L, Ma Q, Yao R and Liu J: Current status and development of anti-PD-1/PD-L1 immunotherapy for lung cancer. Int Immunopharmacol. 79:1060882020. View Article : Google Scholar : PubMed/NCBI

23 

Huard B, Mastrangeli R, Prigent P, Bruniquel D, Donini S, El-Tayar N, Maigret B, Dréano M and Triebel F: Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc Natl Acad Sci USA. 94:5744–5749. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Anderson AC, Joller N and Kuchroo VK: Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation. Immunity. 44:989–1004. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Byun HJ, Jung WW, Lee DS, Kim S, Kim SJ, Park CG, Chung HY and Chun T: Proliferation of activated CD1d-restricted NKT cells is down-modulated by lymphocyte activation gene-3 signaling via cell cycle arrest in S phase. Cell Biol Int. 31:257–262. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Maruhashi T, Okazaki IM, Sugiura D, Takahashi S, Maeda TK, Shimizu K and Okazaki T: LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII. Nat Immunol. 19:1415–1426. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, et al: Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell. 176:334–347.e12. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Kouo T, Huang L, Pucsek AB, Cao M, Solt S, Armstrong T and Jaffee E: Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells. Cancer Immunol Res. 3:412–423. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Tang R, Rangachari M and Kuchroo VK: Tim-3: A co-receptor with diverse roles in T cell exhaustion and tolerance. Semin Immunol. 42:1013022019. View Article : Google Scholar : PubMed/NCBI

30 

Acharya N, Sabatos-Peyton C and Anderson AC: Tim-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer. 8:e0009112020. View Article : Google Scholar : PubMed/NCBI

31 

Das M, Zhu C and Kuchroo VK: Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev. 276:97–111. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T, et al: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 517:386–390. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB and Kuchroo VK: The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 6:1245–1252. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK and Anderson AC: Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 207:2187–2194. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Stanietsky N, Simic H, Arapovic J, Toporik A, Levy O, Novik A, Levine Z, Beiman M, Dassa L, Achdout H, et al: The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci USA. 106:17858–17863. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, Tom I, Ivelja S, Refino CJ, Clark H, et al: The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 10:48–57. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Boles KS, Vermi W, Facchetti F, Fuchs A, Wilson TJ, Diacovo TG, Cella M and Colonna M: A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. Eur J Immunol. 39:695–703. 2009. View Article : Google Scholar : PubMed/NCBI

38 

He Y, Peng H, Sun R, Wei H, Ljunggren HG, Yokoyama WM and Tian Z: Contribution of inhibitory receptor TIGIT to NK cell education. J Autoimmun. 81:1–12. 2017. View Article : Google Scholar : PubMed/NCBI

39 

Johnston RJ, Comps-Agrar L, Hackney J, Yu X, Huseni M, Yang Y, Park S, Javinal V, Chiu H, Irving B, et al: The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell. 26:923–937. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Herzberg B, Campo MJ and Gainor JF: Immune checkpoint inhibitors in non-small cell lung cancer. Oncologist. 22:81–88. 2017. View Article : Google Scholar : PubMed/NCBI

41 

Zhang P, Xiong X, Rolfo C, Du X, Zhang Y, Yang H, Russo A, Devenport M, Zhou P, Liu Y and Zheng P: Mechanism- and immune landscape-based ranking of therapeutic responsiveness of 22 major human cancers to next generation anti-CTLA-4 antibodies. Cancers (Basel). 12:2842020. View Article : Google Scholar : PubMed/NCBI

42 

Kazandjian D, Suzman DL, Blumenthal G, Mushti S, He K, Libeg M, Keegan P and Pazdur R: FDA approval summary: Nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist. 21:634–642. 2016. View Article : Google Scholar : PubMed/NCBI

43 

Akinleye A and Rasool Z: Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol. 12:922019. View Article : Google Scholar : PubMed/NCBI

44 

Mathew M, Enzler T, Shu CA and Rizvi NA: Combining chemotherapy with PD-1 blockade in NSCLC. Pharmacol Ther. 186:130–137. 2018. View Article : Google Scholar : PubMed/NCBI

45 

Cyriac G and Gandhi L: Emerging biomarkers for immune checkpoint inhibition in lung cancer. Semin Cancer Biol. 52:(Pt 2):269–277. 2018. View Article : Google Scholar : PubMed/NCBI

46 

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 366:2443–2454. 2012. View Article : Google Scholar : PubMed/NCBI

47 

Yarchoan M, Albacker LA, Hopkins AC, Montesion M, Murugesan K, Vithayathil TT, Zaidi N, Azad NS, Laheru DA, Frampton GM and Jaffee EM: PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. JCI Insight. 4:e1269082019. View Article : Google Scholar : PubMed/NCBI

48 

Pai-Scherf L, Blumenthal GM, Li H, Subramaniam S, Mishra-Kalyani PS, He K, Zhao H, Yu J, Paciga M, Goldberg KB, et al: FDA approval summary: Pembrolizumab for treatment of metastatic non-small cell lung cancer: First-line therapy and beyond. Oncologist. 22:1392–1399. 2017. View Article : Google Scholar : PubMed/NCBI

49 

Abdel-Rahman O: Correlation between PD-L1 expression and outcome of NSCLC patients treated with anti-PD-1/PD-L1 agents: A meta-analysis. Crit Rev Oncol Hematol. 101:75–85. 2016. View Article : Google Scholar : PubMed/NCBI

50 

Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al: Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 373:123–135. 2015. View Article : Google Scholar : PubMed/NCBI

51 

Davis AA and Patel VG: The role of PD-L1 expression as a predictive biomarker: An analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunother Cancer. 7:2782019. View Article : Google Scholar : PubMed/NCBI

52 

Paver EC, Cooper WA, Colebatch AJ, Ferguson PM, Hill SK, Lum T, Shin JS, O'Toole S, Anderson L, Scolyer RA and Gupta R: Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: A guide to immunohistochemistry implementation and interpretation. Pathology. 53:141–156. 2021. View Article : Google Scholar : PubMed/NCBI

53 

Fournel L, Wu Z, Stadler N, Damotte D, Lococo F, Boulle G, Ségal-Bendirdjian E, Bobbio A, Icard P, Trédaniel J, et al: Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer. Cancer Lett. 464:5–14. 2019. View Article : Google Scholar : PubMed/NCBI

54 

Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L and Rimm DL: Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 94:107–116. 2014. View Article : Google Scholar : PubMed/NCBI

55 

Ilie M, Long-Mira E, Bence C, Butori C, Lassalle S, Bouhlel L, Fazzalari L, Zahaf K, Lalvée S, Washetine K, et al: Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: A potential issue for anti-PD-L1 therapeutic strategies. Ann Oncol. 27:147–153. 2016. View Article : Google Scholar : PubMed/NCBI

56 

Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, West WW, Wu H, Roden AC, et al: A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol. 3:1051–1058. 2017. View Article : Google Scholar : PubMed/NCBI

57 

Büttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, Dietel M, Longshore JW, López-Ríos F, Penault-Llorca F, et al: Programmed death-ligand 1 immunohistochemistry testing: A review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol. 35:3867–3876. 2017. View Article : Google Scholar : PubMed/NCBI

58 

Vilimas T: Measuring tumor mutational burden using whole-exome sequencing. Methods Mol Biol. 2055:63–91. 2020. View Article : Google Scholar : PubMed/NCBI

59 

Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF, Borghaei H, Jolivet J, Horn L, Mates M, et al: First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): Outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J Clin Oncol. 37:992–1000. 2019. View Article : Google Scholar : PubMed/NCBI

60 

Merino DM, McShane LM, Fabrizio D, Funari V, Chen SJ, White JR, Wenz P, Baden J, Barrett JC, Chaudhary R, et al: Establishing guidelines to harmonize tumor mutational burden (TMB): In silico assessment of variation in TMB quantification across diagnostic platforms: Phase I of the Friends of cancer research TMB harmonization project. J Immunother Cancer. 8:e0001472020. View Article : Google Scholar : PubMed/NCBI

61 

Wojas-Krawczyk K, Kalinka E, Grenda A, Krawczyk P and Milanowski J: Beyond PD-L1 markers for lung cancer immunotherapy. Int J Mol Sci. 20:19152019. View Article : Google Scholar : PubMed/NCBI

62 

Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, et al: Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 51:202–206. 2019. View Article : Google Scholar : PubMed/NCBI

63 

Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, Plodkowski A, Long N, Sauter JL, Rekhtman N, et al: Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol. 36:633–641. 2018. View Article : Google Scholar : PubMed/NCBI

64 

Doostparast Torshizi A and Wang K: Next-generation sequencing in drug development: Target identification and genetically stratified clinical trials. Drug Discov Today. 23:1776–1783. 2018. View Article : Google Scholar : PubMed/NCBI

65 

Sa H, Ma K, Gao Y and Wang D: Predictive value of tumor mutation burden in immunotherapy for lung cancer. Zhongguo Fei Ai Za Zhi. 22:380–384. 2019.(In Chinese). PubMed/NCBI

66 

Pisapia P, Malapelle U and Troncone G: Liquid biopsy and lung cancer. Acta Cytol. 63:489–496. 2019. View Article : Google Scholar : PubMed/NCBI

67 

Gandara DR, Paul SM, Kowanetz M, Schleifman E, Zou W, Li Y, Rittmeyer A, Fehrenbacher L, Otto G, Malboeuf C, et al: Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med. 24:1441–1448. 2018. View Article : Google Scholar : PubMed/NCBI

68 

Nie W, Qian J, Xu MD, Gu K, Qian FF, Hu MJ, Lu J, Gan L, Zhang XY, Cao SH, et al: A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab. Oncoimmunology. 9:17310722020. View Article : Google Scholar : PubMed/NCBI

69 

Chen YT, Seeruttun SR, Wu XY and Wang ZX: Maximum somatic allele frequency in combination with blood-based tumor mutational burden to predict the efficacy of atezolizumab in advanced non-small cell lung cancer: A pooled analysis of the randomized POPLAR and OAK studies. Front Oncol. 9:14322019. View Article : Google Scholar : PubMed/NCBI

70 

Zeng DQ, Yu YF, Ou QY, Li XY, Zhong RZ, Xie CM and Hu QG: Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. Oncotarget. 7:13765–13781. 2016. View Article : Google Scholar : PubMed/NCBI

71 

Bodor JN, Boumber Y and Borghaei H: Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer. 126:260–270. 2020. View Article : Google Scholar : PubMed/NCBI

72 

Hurkmans DP, Kuipers ME, Smit J, van Marion R, Mathijssen RHJ, Postmus PE, Hiemstra PS, Aerts JGJV, von der Thüsen JH and van der Burg SH: Tumor mutational load, CD8+ T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients. Cancer Immunol Immunother. 69:771–777. 2020. View Article : Google Scholar : PubMed/NCBI

73 

O'Donnell JS, Long GV, Scolyer RA, Teng MW and Smyth MJ: Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treat Rev. 52:71–81. 2017. View Article : Google Scholar : PubMed/NCBI

74 

Memon H and Patel BM: Immune checkpoint inhibitors in non-small cell lung cancer: A bird's eye view. Life Sci. 233:1167132019. View Article : Google Scholar : PubMed/NCBI

75 

Schumacher TN and Schreiber RD: Neoantigens in cancer immunotherapy. Science. 348:69–74. 2015. View Article : Google Scholar : PubMed/NCBI

76 

Wang S, He Z, Wang X, Li H and Liu XS: Antigen presentation and tumor immunogenicity in cancer immunotherapy response prediction. Elife. 8:e490202019. View Article : Google Scholar : PubMed/NCBI

77 

Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL, et al: Signatures of mutational processes in human cancer. Nature. 500:415–421. 2013. View Article : Google Scholar : PubMed/NCBI

78 

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al: Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 348:124–128. 2015. View Article : Google Scholar : PubMed/NCBI

79 

Martin AM, Nirschl TR, Nirschl CJ, Francica BJ, Kochel CM, van Bokhoven A, Meeker AK, Lucia MS, Anders RA, DeMarzo AM and Drake CG: Paucity of PD-L1 expression in prostate cancer: Innate and adaptive immune resistance. Prostate Cancer Prostatic Dis. 18:325–332. 2015. View Article : Google Scholar : PubMed/NCBI

80 

Leclerc M, Mezquita L, Guillebot De Nerville G, Tihy I, Malenica I, Chouaib S and Mami-Chouaib F: Recent advances in lung cancer immunotherapy: Input of T-cell epitopes associated with impaired peptide processing. Front Immunol. 10:15052019. View Article : Google Scholar : PubMed/NCBI

81 

Garrido C, Paco L, Romero I, Berruguilla E, Stefansky J, Collado A, Algarra I, Garrido F and Garcia-Lora AM: MHC class I molecules act as tumor suppressor genes regulating the cell cycle gene expression, invasion and intrinsic tumorigenicity of melanoma cells. Carcinogenesis. 33:687–693. 2012. View Article : Google Scholar : PubMed/NCBI

82 

Wang X, Schoenhals JE, Li A, Valdecanas DR, Ye H, Zang F, Tang C, Tang M, Liu CG, Liu X, et al: Suppression of type I IFN signaling in tumors mediates resistance to Anti-PD-1 treatment that can be overcome by radiotherapy. Cancer Res. 77:839–850. 2017. View Article : Google Scholar : PubMed/NCBI

83 

Thommen DS, Schreiner J, Müller P, Herzig P, Roller A, Belousov A, Umana P, Pisa P, Klein C, Bacac M, et al: Progression of lung cancer is associated with increased dysfunction of T cells defined by coexpression of multiple inhibitory receptors. Cancer Immunol Res. 3:1344–1355. 2015. View Article : Google Scholar : PubMed/NCBI

84 

Curigliano G, Gelderblom H, Mach N, Doi T, Tai D, Forde PM, Sarantopoulos J, Bedard PL, Lin CC, Hodi FS, et al: Phase I/Ib clinical trial of sabatolimab, an Anti-TIM-3 antibody, alone and in combination with spartalizumab, an Anti-PD-1 antibody, in advanced solid tumors. Clin Cancer Res. 27:3620–3629. 2021. View Article : Google Scholar : PubMed/NCBI

85 

Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, et al: Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 7:105012016. View Article : Google Scholar : PubMed/NCBI

86 

Hellmann MD, Rizvi NA, Goldman JW, Gettinger SN, Borghaei H, Brahmer JR, Ready NE, Gerber DE, Chow LQ, Juergens RA, et al: Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): Results of an open-label, phase 1, multicohort study. Lancet Oncol. 18:31–41. 2017. View Article : Google Scholar : PubMed/NCBI

87 

Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, et al: Nivolumab plus Ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 378:2093–2104. 2018. View Article : Google Scholar : PubMed/NCBI

88 

Bylicki O, Barazzutti H, Paleiron N, Margery J, Assié JB and Chouaïd C: First-line treatment of non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors. BioDrugs. 33:159–171. 2019. View Article : Google Scholar : PubMed/NCBI

89 

Davis M, Conlon K, Bohac GC, Barcenas J, Leslie W, Watkins L, Lamzabi I, Deng Y, Li Y and Plate JM: Effect of pemetrexed on innate immune killer cells and adaptive immune T cells in subjects with adenocarcinoma of the pancreas. J Immunother. 35:629–640. 2012. View Article : Google Scholar : PubMed/NCBI

90 

Javeed A, Ashraf M, Riaz A, Ghafoor A, Afzal S and Mukhtar MM: Paclitaxel and immune system. Eur J Pharm Sci. 38:283–290. 2009. View Article : Google Scholar : PubMed/NCBI

91 

Borghaei H, Langer CJ, Gadgeel S, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, et al: 24-Month overall survival from KEYNOTE-021 Cohort G: Pemetrexed and carboplatin with or without pembrolizumab as first-line therapy for advanced nonsquamous non-small cell lung cancer. J Thorac Oncol. 14:124–129. 2019. View Article : Google Scholar : PubMed/NCBI

92 

Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodríguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, et al: Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 378:2288–2301. 2018. View Article : Google Scholar : PubMed/NCBI

93 

Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, et al: Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 28:2181–2190. 2010. View Article : Google Scholar : PubMed/NCBI

94 

Jarosz-Biej M, Smolarczyk R, Cichoń T and Kułach N: Tumor microenvironment as a ‘game changer’ in cancer radiotherapy. Int J Mol Sci. 20:32122019. View Article : Google Scholar : PubMed/NCBI

95 

Barker HE, Paget JT, Khan AA and Harrington KJ: The tumour microenvironment after radiotherapy: Mechanisms of resistance and recurrence. Nat Rev Cancer. 15:409–425. 2015. View Article : Google Scholar : PubMed/NCBI

96 

Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR and Fu YX: Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 124:687–695. 2014. View Article : Google Scholar : PubMed/NCBI

97 

Gong X, Li X, Jiang T, Xie H, Zhu Z, Zhou F and Zhou C: Combined radiotherapy and anti-PD-L1 antibody synergistically enhances antitumor effect in non-small cell lung cancer. J Thorac Oncol. 12:1085–1097. 2017. View Article : Google Scholar : PubMed/NCBI

98 

Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, et al: Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer: Results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA Oncol. 5:1276–1282. 2019. View Article : Google Scholar : PubMed/NCBI

99 

Li JX, Huang JM, Jiang ZB, Li RZ, Sun A, Lai-Han Leung E and Yan PY: Current clinical progress of PD-1/PD-L1 immunotherapy and potential combination treatment in non-small cell lung cancer. Integr Cancer Ther. 18:15347354198900202019. View Article : Google Scholar : PubMed/NCBI

100 

Habas K, Nganwuchu C, Shahzad F, Gopalan R, Haque M, Rahman S, Majumder AA and Nasim T: Resolution of coronavirus disease 2019 (COVID-19). Expert Rev Anti Infect Ther. 18:1201–1211. 2020. View Article : Google Scholar : PubMed/NCBI

101 

DU HZ, Hou XY, Miao YH, Huang BS and Liu DH: Traditional Chinese Medicine: An effective treatment for 2019 novel coronavirus pneumonia (NCP). Chin J Nat Med. 18:206–210. 2020.PubMed/NCBI

102 

Wood SL, Pernemalm M, Crosbie PA and Whetton AD: The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev. 40:558–566. 2014. View Article : Google Scholar : PubMed/NCBI

103 

Wang Y, Zhang Q, Chen Y, Liang CL, Liu H, Qiu F and Dai Z: Antitumor effects of immunity-enhancing traditional Chinese medicine. Biomed Pharmacother. 121:1095702020. View Article : Google Scholar : PubMed/NCBI

104 

Liao CH, Yong CY, Lai GM, Chow JM, Cheng CF, Fang CL, Lin PC, Chang CL, Zheng YM, Chuang SE, et al: Astragalus polysaccharide (PG2) suppresses macrophage migration inhibitory factor and aggressiveness of lung adenocarcinoma cells. Am J Chin Med. 48:1491–1509. 2020. View Article : Google Scholar : PubMed/NCBI

105 

Li W, Hu X, Wang S, Jiao Z, Sun T, Liu T and Song K: Characterization and anti-tumor bioactivity of astragalus polysaccharides by immunomodulation. Int J Biol Macromol. 145:985–997. 2020. View Article : Google Scholar : PubMed/NCBI

106 

Bamodu OA, Kuo KT, Wang CH, Huang WC, Wu ATH, Tsai JT, Lee KY, Yeh CT and Wang LS: Astragalus polysaccharides (PG2) enhances the M1 polarization of macrophages, functional maturation of dendritic cells, and T cell-mediated anticancer immune responses in patients with lung cancer. Nutrients. 11:22642019. View Article : Google Scholar : PubMed/NCBI

107 

Wang HB, Zheng QY, Qian DH, Fang J and Ju DW: Effects of Phytolacca acinosa polysaccharides I on immune function in mice. Zhongguo Yao Li Xue Bao. 14:243–246. 1993.PubMed/NCBI

108 

Chen Y, Wang Y, Xu L, Zhu W, Xu C, Xu M, Guo L, Hu W, Xu D, Jing R, et al: Influence of total glucosides of paeony on PD-1/PD-L1 expression in primary Sjögren's syndrome. Int J Rheum Dis. 22:200–206. 2019. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma L, Li J, Tang L, Li R, Yang J, Sun A, Leung EL and Yan P: Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review). Oncol Lett 22: 787, 2021.
APA
Ma, L., Li, J., Tang, L., Li, R., Yang, J., Sun, A. ... Yan, P. (2021). Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review). Oncology Letters, 22, 787. https://doi.org/10.3892/ol.2021.13048
MLA
Ma, L., Li, J., Tang, L., Li, R., Yang, J., Sun, A., Leung, E. L., Yan, P."Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review)". Oncology Letters 22.5 (2021): 787.
Chicago
Ma, L., Li, J., Tang, L., Li, R., Yang, J., Sun, A., Leung, E. L., Yan, P."Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review)". Oncology Letters 22, no. 5 (2021): 787. https://doi.org/10.3892/ol.2021.13048
Copy and paste a formatted citation
x
Spandidos Publications style
Ma L, Li J, Tang L, Li R, Yang J, Sun A, Leung EL and Yan P: Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review). Oncol Lett 22: 787, 2021.
APA
Ma, L., Li, J., Tang, L., Li, R., Yang, J., Sun, A. ... Yan, P. (2021). Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review). Oncology Letters, 22, 787. https://doi.org/10.3892/ol.2021.13048
MLA
Ma, L., Li, J., Tang, L., Li, R., Yang, J., Sun, A., Leung, E. L., Yan, P."Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review)". Oncology Letters 22.5 (2021): 787.
Chicago
Ma, L., Li, J., Tang, L., Li, R., Yang, J., Sun, A., Leung, E. L., Yan, P."Immune checkpoints and immunotherapy in non‑small cell lung cancer: Novel study progression, challenges and solutions (Review)". Oncology Letters 22, no. 5 (2021): 787. https://doi.org/10.3892/ol.2021.13048
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team