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
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
January-2025 Volume 22 Issue 1

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
January-2025 Volume 22 Issue 1

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

Factors associated with immune‑related severe adverse events (Review)

  • Authors:
    • Zhenzhen Su
    • Miaomiao Guan
    • Liyan Zhang
    • Xuemin Lian
  • View Affiliations / Copyright

    Affiliations: School of Nursing, Peking University, Beijing 100191, P.R. China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
    Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 3
    |
    Published online on: October 31, 2024
       https://doi.org/10.3892/mco.2024.2798
  • 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

Immune checkpoint inhibitors (ICIs) are frequently used in cancer treatment. Despite their clinical benefits, they can also cause a wide range of immune‑related adverse events (ir‑AEs). The overall incidence of irAEs in cancer patients treated with immunotherapy ranges from 70‑90%, while that of immune‑related severe adverse events (ir‑SAEs) is 10‑43%. ir‑SAEs pose a significant risk to patient safety as they are extremely frequent and lethal. Due to non‑specific manifestations, rapid progression and significant morbidity, it is essential to identify factors associated with ir‑SAEs early to predict high‑risk groups for treatment safety. However, less information is available on the factors causing ir‑SAEs, and further research is needed. The present study reviews the factors associated with ir‑SAEs in terms of demographic characteristics, disease‑related information and laboratory examinations to provide a clinical reference. In terms of demographic characteristics, age, body mass index, smoking, ethnicity and cancer family history may influence the incidence of ir‑SAEs. Regarding disease‑related information, the risks factors associated with ir‑SAEs may include disease history, treatment regimen and cancer type. For laboratory examinations, risk factors associated with ir‑SAEs include the laboratory examination parameters of peripheral blood cells, immunocytes, cytokines/chemokines, genetics, gut microbia, proteins and brain injury markers. All of these risk factors can stimulate the body's inflammatory response, leading to over proliferation of T cells and other inflammatory factors. In addition, the use of ICIs may disrupt gut microbial homeostasis and dysregulate the pre‑existing intestinal ecology, which may therefore trigger inflammatory signaling pathways, affect overall immune function and increase the occurrence of ir‑SAEs. In response to the aforementioned risk factors, it is recommended that medical professionals incorporate their analysis into routine patient testing for early identification of patient ir‑SAEs and to create early individualized interventions to improve the safety for immunotherapy patients.
View Figures

Figure 1

View References

1 

Lee JB, Kim HR and Ha SJ: Immune checkpoint inhibitors in 10 years: Contribution of basic research and clinical application in cancer immunotherapy. Immune Netw. 22(e2)2022.PubMed/NCBI View Article : Google Scholar

2 

Carlino MS, Larkin J and Long GV: Immune checkpoint inhibitors in melanoma. Lancet. 398:1002–1014. 2021.PubMed/NCBI View Article : Google Scholar

3 

Xia L, Liu Y and Wang Y: PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: Current status and future directions. Oncologist. 24 (Suppl 1):S31–S41. 2019.PubMed/NCBI View Article : Google Scholar

4 

Postow MA, Sidlow R and Hellmann MD: Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 378:158–168. 2018.PubMed/NCBI View Article : Google Scholar

5 

Zhang L, Reynolds KL, Lyon AR, Palaskas N and Neilan TG: The evolving immunotherapy landscape and the epidemiology, diagnosis, and management of cardiotoxicity: JACC: CardioOncology primer. JACC CardioOncol. 3:35–47. 2021.PubMed/NCBI View Article : Google Scholar

6 

Khoja L, Day D, Wei-Wu Chen T, Siu LL and Hansen AR: Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: A systematic review. Ann Oncol. 28:2377–2385. 2017.PubMed/NCBI View Article : Google Scholar

7 

Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, et al: Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med. 383:1328–1339. 2020.PubMed/NCBI View Article : Google Scholar

8 

Zhou C, Li M, Wang Z, An D and Li B: Adverse events of immunotherapy in non-small cell lung cancer: A systematic review and network meta-analysis. Int Immunopharmacol. 102(108353)2022.PubMed/NCBI View Article : Google Scholar

9 

Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, et al: Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis. JAMA Oncol. 4:1721–1728. 2018.PubMed/NCBI View Article : Google Scholar

10 

Heymach JV, Mitsudomi T, Harpole D, Aperghis M, Jones S, Mann H, Fouad TM and Reck M: Design and rationale for a phase III, double-blind, placebo-controlled study of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab for the treatment of patients with resectable stages II and III non-small-cell lung cancer: The AEGEAN trial. Clin Lung Cancer. 23:e247–e251. 2022.PubMed/NCBI View Article : Google Scholar

11 

Rodríguez-Abreu D, Powell SF, Hochmair MJ, Gadgeel S, Esteban E, Felip E, Speranza G, De Angelis F, Dómine M, Cheng SY, et al: Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: Protocol-specified final analysis from KEYNOTE-189. Ann Oncol. 32:881–895. 2021.PubMed/NCBI View Article : Google Scholar

12 

Bernstein MB, Krishnan S, Hodge JW and Chang JY: Immunotherapy and stereotactic ablative radiotherapy (ISABR): A curative approach? Nat Rev Clin Oncol. 13:516–524. 2016.PubMed/NCBI View Article : Google Scholar

13 

Grant MJ, Herbst RS and Goldberg SB: Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC. Nat Rev Clin Oncol. 18:625–644. 2021.PubMed/NCBI View Article : Google Scholar

14 

Rubio-Infante N, Ramírez-Flores YA, Castillo EC, Lozano O, García-Rivas G and Torre-Amione G: Cardiotoxicity associated with immune checkpoint inhibitor therapy: A meta-analysis. Eur J Heart Fail. 23:1739–1747. 2021.PubMed/NCBI View Article : Google Scholar

15 

Baldini C, Martin Romano P, Voisin AL, Danlos FX, Champiat S, Laghouati S, Kfoury M, Vincent H, Postel-Vinay S, Varga A, et al: Impact of aging on immune-related adverse events generated by anti-programmed death (ligand)PD-(L)1 therapies. Eur J Cancer. 129:71–79. 2020.PubMed/NCBI View Article : Google Scholar

16 

Shah KP, Song H, Ye F, Moslehi JJ, Balko JM, Salem JE and Johnson DB: Demographic factors associated with toxicity in patients treated with anti-programmed cell death-1 therapy. Cancer Immunol Res. 8:851–855. 2020.PubMed/NCBI View Article : Google Scholar

17 

Kanjanapan Y and Yip D: Characteristics and risk factors for microbial infections during cancer immune checkpoint therapy. Cancer Med. 9:9027–9035. 2020.PubMed/NCBI View Article : Google Scholar

18 

Ksienski D, Truong PT, Croteau NS, Chan A, Sonke E, Patterson T, Clarkson M, Hackett S and Lesperance M: Immune related adverse events and treatment discontinuation in patients older and younger than 75 years with advanced melanoma receiving nivolumab or pembrolizumab. J Geriatr Oncol. 13:220–227. 2022.PubMed/NCBI View Article : Google Scholar

19 

Guzman-Prado Y, Ben Shimol J and Samson O: Body mass index and immune-related adverse events in patients on immune checkpoint inhibitor therapies: A systematic review and meta-analysis. Cancer Immunol Immunother. 70:89–100. 2021.PubMed/NCBI View Article : Google Scholar

20 

Assumpção JAF, Pasquarelli-do-Nascimento G, Duarte MSV, Bonamino MH and Magalhães KG: The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy. J Biomed Sci. 29(12)2022.PubMed/NCBI View Article : Google Scholar

21 

Cortellini A, Bersanelli M, Santini D, Buti S, Tiseo M, Cannita K, Perrone F, Giusti R, De Tursi M, Zoratto F, et al: Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events. Eur J Cancer. 128:17–26. 2020.PubMed/NCBI View Article : Google Scholar

22 

De Filippi R, Morabito F, Santoro A, Tripepi G, D'Alò F, Rigacci L, Ricci F, Morelli E, Zinzani PL and Pinto A: Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab. J Transl Med. 19(489)2021.PubMed/NCBI View Article : Google Scholar

23 

Wood C, Lopez G, Zhao L, Li M, Surya N, Patel S, Grogan M, Bertino E, Shields P, He K, et al: P78.05 Patterns of irAE during first line pembrolizumab for NSCLC: Incidence, risk factors, and impact on clinical outcome. J Thorac Oncol. 16 (Suppl 1):S639–S640. 2021.

24 

Muthumalage T and Rahman I: Pulmonary immune response regulation, genotoxicity, and metabolic reprogramming by menthol- and tobacco-flavored e-cigarette exposures in mice. Toxicol Sci. 193:146–165. 2023.PubMed/NCBI View Article : Google Scholar

25 

Abdelrahim M, Mamlouk O, Lin H, Lin J, Page V, Abdel-Wahab N, Swan J, Selamet U, Yee C, Diab A, et al: Incidence, predictors, and survival impact of acute kidney injury in patients with melanoma treated with immune checkpoint inhibitors: A 10-year single-institution analysis. Oncoimmunology. 10(1927313)2021.PubMed/NCBI View Article : Google Scholar

26 

GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: A systematic analysis for the global burden of disease study 2017. Lancet. 395:709–733. 2020.PubMed/NCBI View Article : Google Scholar

27 

Cortellini A, Buti S, Bersanelli M, Giusti R, Perrone F, Di Marino P, Tinari N, De Tursi M, Grassadonia A, Cannita K, et al: Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: The multicenter FAMI-L1 study. Oncoimmunology. 9(1710389)2020.PubMed/NCBI View Article : Google Scholar

28 

Sorah JD, Rose TL, Radhakrishna R, Derebail VK and Milowsky MI: Incidence and prediction of immune checkpoint inhibitor-related nephrotoxicity. J Immunother. 44:127–131. 2021.PubMed/NCBI View Article : Google Scholar

29 

Akturk HK, Alkanani A, Zhao Z, Yu L and Michels AW: PD-1 inhibitor immune-related adverse events in patients with preexisting endocrine autoimmunity. J Clin Endocrinol Metab. 103:3589–3592. 2018.PubMed/NCBI View Article : Google Scholar

30 

Haanen J, Ernstoff MS, Wang Y, Menzies AM, Puzanov I, Grivas P, Larkin J, Peters S, Thompson JA and Obeid M: Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy. Ann Oncol. 31:724–744. 2020.PubMed/NCBI View Article : Google Scholar

31 

Tang K, Tiu BC, Wan G, Zhang S, Nguyen N, Leung B, Gusev A, Reynolds KL, Kwatra SG and Semenov YR: Pre-existing autoimmune disease and mortality in patients treated with anti-PD-1 and Anti-PD-L1 therapy. J Natl Cancer Inst. 114:1200–1202. 2022.PubMed/NCBI View Article : Google Scholar

32 

Oren O, Yang EH, Molina JR, Bailey KR, Blumenthal RS and Kopecky SL: Cardiovascular health and outcomes in cancer patients receiving immune checkpoint inhibitors. Am J Cardiol. 125:1920–1926. 2020.PubMed/NCBI View Article : Google Scholar

33 

Noseda R, Ruinelli L, Gaag LCV and Ceschi A: Pre-existing cardiovascular conditions as clinical predictors of myocarditis reporting with immune checkpoint inhibitors: A vigibase study. Cancers (Basel). 12(3480)2020.PubMed/NCBI View Article : Google Scholar

34 

Kim PH, Suh CH, Kim HS, Kim KW, Kim DY, Lee EQ, Aizer AA, Guenette JP and Huang RY: Immune checkpoint inhibitor with or without radiotherapy in melanoma patients with brain metastases: A systematic review and meta-analysis. Korean J Radiol. 22:584–595. 2021.PubMed/NCBI View Article : Google Scholar

35 

Miyashita H, Mikami T, Satoi S, Cruz C and Galsky MD: Incidence and risk of colitis with programmed death 1 versus programmed death ligand 1 inhibitors for the treatment of cancer. J Immunother. 43:291–298. 2020.PubMed/NCBI View Article : Google Scholar

36 

Luoma AM, Suo S, Williams HL, Sharova T, Sullivan K, Manos M, Bowling P, Hodi FS, Rahma O, Sullivan RJ, et al: Molecular pathways of colon inflammation induced by cancer immunotherapy. Cell. 182:655–671.e22. 2020.PubMed/NCBI View Article : Google Scholar

37 

Huang YF, Xie WJ, Fan HY and Du J: Comparative risks of high-grade adverse events among FDA-approved systemic therapies in advanced melanoma: Systematic review and network meta-analysis. Front Oncol. 10(571135)2020.PubMed/NCBI View Article : Google Scholar

38 

Zheng J, Huang B, Xiao L, Wu M and Li J: Treatment- and immune-related adverse events of immune checkpoint inhibitors in esophageal or gastroesophageal junction cancer: A network meta-analysis of randomized controlled trials. Front Oncol. 12(821626)2022.PubMed/NCBI View Article : Google Scholar

39 

Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB and Lee P: Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: A secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol. 18:895–903. 2017.PubMed/NCBI View Article : Google Scholar

40 

Quhal F, Mori K, Bruchbacher A, Resch I, Mostafaei H, Pradere B, Schuettfort VM, Laukhtina E, Egawa S, Fajkovic H, et al: First-line Immunotherapy-based combinations for metastatic renal cell carcinoma: A systematic review and network meta-analysis. Eur Urol Oncol. 4:755–765. 2021.PubMed/NCBI View Article : Google Scholar

41 

Schoenfeld AJ, Arbour KC, Rizvi H, Iqbal AN, Gadgeel SM, Girshman J, Kris MG, Riely GJ, Yu HA and Hellmann MD: Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. Ann Oncol. 30:839–844. 2019.PubMed/NCBI View Article : Google Scholar

42 

Que S, Feng W and Xu Y: Progress on immunotherapy combined with chemotherapy, radiotherapy and targeted therapy for brain metastasis of small cell lung cancer. J Chin Oncol. 30:177–185. 2024.

43 

Zhang Q and Xu H: Meta-analysis of efficacy and adverse effects of different combination schemes of PD-1/PD-L1 inhibitors in the treatment of ovarian cancer. Chin J Clin Obstet Gynecol. 25:292–297. 2024.

44 

Cheng Y, Yang F and Zhang Y: Research progress of phototherapy combined with immune checkpoint inhibitors in the treatment of tumors. Chin J Cancer Biother. 31:626–631. 2024.

45 

Lizotte PH, Hong RL, Luster TA, Cavanaugh ME, Taus LJ, Wang S, Dhaneshwar A, Mayman N, Yang A, Kulkarni M, et al: A high-throughput immune-oncology screen identifies EGFR inhibitors as potent enhancers of antigen-specific cytotoxic T-lymphocyte tumor cell killing. Cancer Immunol Res. 6:1511–1523. 2018.PubMed/NCBI View Article : Google Scholar

46 

Mazzola R, Jereczek-Fossa BA, Franceschini D, Tubin S, Filippi AR, Tolia M, Lancia A, Minniti G, Corradini S, Arcangeli S, et al: Oligometastasis and local ablation in the era of systemic targeted and immunotherapy. Radiat Oncol. 15(92)2020.PubMed/NCBI View Article : Google Scholar

47 

Galluzzi L, Spranger S, Fuchs E and López-Soto A: WNT signaling in cancer immunosurveillance. Trends Cell Biol. 29:44–65. 2019.PubMed/NCBI View Article : Google Scholar

48 

Du S, Zhou L, Alexander GS, Park K, Yang L, Wang N, Zaorsky NG, Ma X, Wang Y, Dicker AP and Lu B: PD-1 modulates radiation-induced cardiac toxicity through cytotoxic T lymphocytes. J Thorac Oncol. 13:510–520. 2018.PubMed/NCBI View Article : Google Scholar

49 

L'Orphelin JM, Varey E, Khammari A, Dreno B and Dompmartin A: Severe late-onset grade III-IV adverse events under immunotherapy: A retrospective study of 79 cases. Cancers (Basel). 13(4928)2021.PubMed/NCBI View Article : Google Scholar

50 

Ruste V, Goldschmidt V, Laparra A, Messayke S, Danlos FX, Romano-Martin P, Champiat S, Voisin AL, Baldini C, Massard C, et al: The determinants of very severe immune-related adverse events associated with immune checkpoint inhibitors: A prospective study of the French REISAMIC registry. Eur J Cancer. 158:217–224. 2021.PubMed/NCBI View Article : Google Scholar

51 

Brumberger ZL, Branch ME, Klein MW, Seals A, Shapiro MD and Vasu S: Cardiotoxicity risk factors with immune checkpoint inhibitors. Cardiooncology. 8(3)2022.PubMed/NCBI View Article : Google Scholar

52 

Sher AF, Golshani GM and Wu S: Fatal adverse events associated with pembrolizumab in cancer patients: A meta-analysis. Cancer Invest. 38:130–138. 2020.PubMed/NCBI View Article : Google Scholar

53 

Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX and Finn RS: Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 19:151–172. 2022.PubMed/NCBI View Article : Google Scholar

54 

Lou S, Cao Z, Chi W, Wang X, Feng M, Lin L, Ding Y, Liu K, Qu L, Zhao G, et al: The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB. Front Pharmacol. 14(1164309)2023.PubMed/NCBI View Article : Google Scholar

55 

Liu W, Liu Y, Ma F, Sun B, Wang Y, Luo J, Liu M and Luo Z: Peripheral blood markers associated with immune-related adverse effects in patients who had advanced non-small cell lung cancer treated with PD-1 inhibitors. Cancer Manag Res. 13:765–771. 2021.PubMed/NCBI View Article : Google Scholar

56 

Zhao L, Li Y, Jiang N, Song X, Xu J, Zhu X, Chen C, Kong C, Wang X, Zong D, et al: Association of blood biochemical indexes and antibiotic exposure with severe immune-related adverse events in patients with advanced cancers receiving PD-1 inhibitors. J Immunother. 45:210–216. 2022.PubMed/NCBI View Article : Google Scholar

57 

Takada S, Murooka H, Tahatsu K, Yanase M, Umehara K, Hashishita H, Toru H, Satoru M, Sagawa T, Fujikawa K, et al: Identifying early predictive markers for immune-related adverse events in nivolumab-treated patients with renal cell carcinoma and gastric cancer. Asian Pac J Cancer Prev. 23:695–701. 2022.PubMed/NCBI View Article : Google Scholar

58 

Zhang W, Tan Y, Li Y and Liu J: Neutrophil to Lymphocyte ratio as a predictor for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis. Front Immunol. 14(1234142)2023.PubMed/NCBI View Article : Google Scholar

59 

Drobni ZD, Zafar A, Zubiri L, Zlotoff DA, Alvi RM, Lee C, Hartmann S, Gilman HK, Villani AC, Nohria A, et al: Decreased absolute lymphocyte count and increased neutrophil/lymphocyte ratio with immune checkpoint inhibitor-associated myocarditis. J Am Heart Assoc. 9(e018306)2020.PubMed/NCBI View Article : Google Scholar

60 

Zhou JG, Wong AH, Wang H, Tan F, Chen X, Jin SH, He SS, Shen G, Wang YJ, Frey B, et al: Elucidation of the application of blood test biomarkers to predict immune-related adverse events in atezolizumab-treated NSCLC patients using machine learning methods. Front Immunol. 13(862752)2022.PubMed/NCBI View Article : Google Scholar

61 

Lozano AX, Chaudhuri AA, Nene A, Bacchiocchi A, Earland N, Vesely MD, Usmani A, Turner BE, Steen CB, Luca BA, et al: T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma. Nat Med. 28:353–362. 2022.PubMed/NCBI View Article : Google Scholar

62 

Johnson DB, McDonnell WJ, Gonzalez-Ericsson PI, Al-Rohil RN, Mobley BC, Salem JE, Wang DY, Sanchez V, Wang Y, Chastain CA, et al: A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis. Nat Med. 25:1243–1250. 2019.PubMed/NCBI View Article : Google Scholar

63 

Zamora C, Riudavets M, Anguera G, Alserawan L, Sullivan I, Barba A, Serra J, Ortiz MA, Gallardo P, Perea L, et al: Circulating leukocyte-platelet complexes as a predictive biomarker for the development of immune-related adverse events in advanced non-small cell lung cancer patients receiving anti-PD-(L)1 blocking agents. Cancer Immunol Immunother. 70:1691–1704. 2021.PubMed/NCBI View Article : Google Scholar

64 

Das R, Bar N, Ferreira M, Newman AM, Zhang L, Bailur JK, Bacchiocchi A, Kluger H, Wei W, Halaban R, et al: Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest. 128:715–720. 2018.PubMed/NCBI View Article : Google Scholar

65 

Chao Y, Zhou J, Hsu S, Ding N, Li J, Zhang Y, Xu X, Tang X, Wei T, Zhu Z, et al: Risk factors for immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer. Transl Lung Cancer Res. 11:295–306. 2022.PubMed/NCBI View Article : Google Scholar

66 

Costantini A, Takam Kamga P, Julie C, Corjon A, Dumenil C, Dumoulin J, Ouaknine J, Giraud V, Chinet T, Rottman M, et al: Plasma biomarkers screening by multiplex ELISA assay in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors. Cancers (Basel). 13(97)2020.PubMed/NCBI View Article : Google Scholar

67 

Kaminska P, Tempes A, Scholz E and Malik AR: Cytokines on the way to secretion. Cytokine Growth Factor Rev. 79:52–65. 2024.PubMed/NCBI View Article : Google Scholar

68 

Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA and Liu G: Cytokines: From clinical significance to quantification. Adv Sci (Weinh). 8(e2004433)2021.PubMed/NCBI View Article : Google Scholar

69 

Marschner D, Falk M, Javorniczky NR, Hanke-Müller K, Rawluk J, Schmitt-Graeff A, Simonetta F, Haring E, Dicks S, Ku M, et al: MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors. JCI Insight. 5(e132334)2020.PubMed/NCBI View Article : Google Scholar

70 

Friedlander P, Wood K, Wassmann K, Christenfeld AM, Bhardwaj N and Oh WK: A whole-blood RNA transcript-based gene signature is associated with the development of CTLA-4 blockade-related diarrhea in patients with advanced melanoma treated with the checkpoint inhibitor tremelimumab. J Immunother Cancer. 6(90)2018.PubMed/NCBI View Article : Google Scholar

71 

Refae S, Gal J, Ebran N, Otto J, Borchiellini D, Peyrade F, Chamorey E, Brest P, Milano G and Saada-Bouzid E: Correction to: Germinal Immunogenetics predict treatment outcome for PD-1/PD-L1 checkpoint inhibitors. Invest New Drugs. 39:287–292. 2021.PubMed/NCBI View Article : Google Scholar

72 

Liu W, Ma F, Sun B, Liu Y, Tang H, Luo J, Chen H and Luo Z: Intestinal microbiome associated with immune-related adverse events for patients treated with anti-PD-1 inhibitors, a real-world study. Front Immunol. 12(756872)2021.PubMed/NCBI View Article : Google Scholar

73 

Levy M, Kolodziejczyk AA, Thaiss CA and Elinav E: Dysbiosis and the immune system. Nat Rev Immunol. 17:219–232. 2017.PubMed/NCBI View Article : Google Scholar

74 

Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, Ishida M, Hiai H, Matsumori A, Minato N and Honjo T: Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 9:1477–1483. 2003.PubMed/NCBI View Article : Google Scholar

75 

Ji C, Roy MD, Golas J, Vitsky A, Ram S, Kumpf SW, Martin M, Barletta F, Meier WA, Hooper AT, et al: Myocarditis in cynomolgus monkeys following treatment with immune checkpoint inhibitors. Clin Cancer Res. 25:4735–4748. 2019.PubMed/NCBI View Article : Google Scholar

76 

Bjursten S, Pandita A, Zhao Z, Fröjd C, Ny L, Jensen C, Ullerstam T, Jespersen H, Borén J, Levin M, et al: Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis. J Immunother Cancer. 9(e002732)2021.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Su Z, Guan M, Zhang L and Lian X: Factors associated with immune‑related severe adverse events (Review). Mol Clin Oncol 22: 3, 2025.
APA
Su, Z., Guan, M., Zhang, L., & Lian, X. (2025). Factors associated with immune‑related severe adverse events (Review). Molecular and Clinical Oncology, 22, 3. https://doi.org/10.3892/mco.2024.2798
MLA
Su, Z., Guan, M., Zhang, L., Lian, X."Factors associated with immune‑related severe adverse events (Review)". Molecular and Clinical Oncology 22.1 (2025): 3.
Chicago
Su, Z., Guan, M., Zhang, L., Lian, X."Factors associated with immune‑related severe adverse events (Review)". Molecular and Clinical Oncology 22, no. 1 (2025): 3. https://doi.org/10.3892/mco.2024.2798
Copy and paste a formatted citation
x
Spandidos Publications style
Su Z, Guan M, Zhang L and Lian X: Factors associated with immune‑related severe adverse events (Review). Mol Clin Oncol 22: 3, 2025.
APA
Su, Z., Guan, M., Zhang, L., & Lian, X. (2025). Factors associated with immune‑related severe adverse events (Review). Molecular and Clinical Oncology, 22, 3. https://doi.org/10.3892/mco.2024.2798
MLA
Su, Z., Guan, M., Zhang, L., Lian, X."Factors associated with immune‑related severe adverse events (Review)". Molecular and Clinical Oncology 22.1 (2025): 3.
Chicago
Su, Z., Guan, M., Zhang, L., Lian, X."Factors associated with immune‑related severe adverse events (Review)". Molecular and Clinical Oncology 22, no. 1 (2025): 3. https://doi.org/10.3892/mco.2024.2798
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