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Review

PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review)

  • Authors:
    • Shuangcui Wang
    • Changyu Liu
    • Chenxin Yang
    • Yutong Jin
    • Qian Cui
    • Dong Wang
    • Ting Ge
    • Guixin He
    • Wentao Li
    • Guan Zhang
    • Aqing Liu
    • Ying Xia
    • Yunhe Liu
    • Jianchun Yu
  • View Affiliations / Copyright

    Affiliations: Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China, Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China
  • Article Number: 567
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    Published online on: September 26, 2024
       https://doi.org/10.3892/ol.2024.14700
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Abstract

T cells play an important role in cancer, and energy metabolism can determine both the proliferation and differentiation of T cells. The inhibition of immune checkpoint molecules programmed cell death protein 1 (PD‑1) and cytotoxic T‑lymphocyte associated protein 4 (CTLA‑4) are a promising cancer treatment. In recent years, research on CD28 has increased. Although numerous reports involve CD28 and its downstream PI3K/AKT/mTOR signaling mechanisms in T cell metabolism, they have not yet been elucidated. A literature search strategy was used for the databases PubMed, Scopus, Web of Science and Cochrane Library to ensure broad coverage of medical and scientific literature, using a combination of keywords including, but not limited to, ‘lung cancer’ and ‘immunotherapy’. Therefore, the present study reviewed the interaction and clinical application of the PD‑1/CTLA‑4/CD28 and PI3K/AKT/mTOR pathways in T cells, aiming to provide a theoretical basis for immunotherapy in clinical cancer patients.
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1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Shi H, Zhang W, Zhang L, Zheng Y and Dong T: Comparison of different predictive biomarker testing assays for PD-1/PD-L1 checkpoint inhibitors response: A systematic review and network meta-analysis. Front Immunol. 14:12652022023. View Article : Google Scholar : PubMed/NCBI

3 

Qiu J, Cheng Z, Jiang Z, Gan L, Zhang Z and Xie Z: Immunomodulatory precision: A narrative review exploring the critical role of immune checkpoint inhibitors in cancer treatment. Int J Mol Sci. 25:54902024. View Article : Google Scholar : PubMed/NCBI

4 

Choi SH, Mani M, Kim J, Cho WJ, Martin TFJ, Kim JH, Chu HS, Jeong WJ, Won YW, Lee BJ, et al: DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 therapy. Cell Death Discov. 10:2602024. View Article : Google Scholar : PubMed/NCBI

5 

Shen X, Yang J, Qian G, Sheng M, Wang Y, Li G and Yan J: Treatment-related adverse events of immune checkpoint inhibitors in clinical trials: A systematic review and meta-analysis. Front Oncol. 14:13917242024. View Article : Google Scholar : PubMed/NCBI

6 

Han Y, Liu D and Li L: PD-1/PD-L1 pathway: Current researches in cancer. Am J Cancer Res. 10:727–742. 2020.PubMed/NCBI

7 

Chen C, Wang Z and Qin Y: CRISPR/Cas9 system: Recent applications in immuno-oncology and cancer immunotherapy. Exp Hematol Oncol. 12:952023. View Article : Google Scholar : PubMed/NCBI

8 

Guo C, Chen S, Liu W, Ma Y, Li J, Fisher PB, Fang X and Wang XY: Immunometabolism: A new target for improving cancer immunotherapy. Adv Cancer Res. 143:195–253. 2019. View Article : Google Scholar : PubMed/NCBI

9 

Lim SA, Su W, Chapman NM and Chi H: Lipid metabolism in T cell signaling and function. Nat Chem Biol. 18:470–481. 2022. View Article : Google Scholar : PubMed/NCBI

10 

Mafi S, Mansoori B, Taeb S, Sadeghi H, Abbasi R, Cho WC and Rostamzadeh D: mTOR-Mediated regulation of immune responses in cancer and tumor microenvironment. Front Immunol. 12:7741032021. View Article : Google Scholar : PubMed/NCBI

11 

He J, Zeng F, Jin XI, Liang L, Gao M, Li W, Li G and Zhou Y: YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells. Oncol Res. 31:615–630. 2023. View Article : Google Scholar : PubMed/NCBI

12 

Liang Y, Wang X, Wang H, Yang W, Yi P, Soong L, Cong Y, Cai J, Fan X and Sun J: IL-33 activates mTORC1 and modulates glycolytic metabolism in CD8+ T cells. Immunology. 165:61–73. 2022. View Article : Google Scholar : PubMed/NCBI

13 

Kruse B, Buzzai AC, Shridhar N, Braun AD, Gellert S, Knauth K, Pozniak J, Peters J, Dittmann P, Mengoni M, et al: CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours. Nature. 618:1033–1040. 2023. View Article : Google Scholar : PubMed/NCBI

14 

Saxena A, Dagur PK and Biancotto A: Multiparametric flow cytometry analysis of naïve, memory, and effector T cells. Methods Mol Biol. 2032:129–140. 2019. View Article : Google Scholar : PubMed/NCBI

15 

Notarbartolo S and Abrignani S: Human T lymphocytes at tumor sites. Semin Immunopathol. 44:883–901. 2022. View Article : Google Scholar : PubMed/NCBI

16 

Goronzy JJ and Weyand CM: Mechanisms underlying T cell ageing. Nat Rev Immunol. 19:573–583. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Zander R, Schauder D, Xin G, Nguyen C, Wu X, Zajac A and Cui W: CD4+ T cell help is required for the formation of a Cytolytic CD8+ T cell subset that protects against chronic infection and cancer. Immunity. 51:1028–1042.e4. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Omilusik KD and Goldrath AW: Remembering to remember: T cell memory maintenance and plasticity. Curr Opin Immunol. 58:89–97. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Fazeli P, Kalani M and Hosseini M: T memory stem cell characteristics in autoimmune diseases and their promising therapeutic values. Front Immunol. 14:12042312023. View Article : Google Scholar : PubMed/NCBI

20 

Liu Q, Sun Z and Chen L: Memory T cells: Strategies for optimizing tumor immunotherapy. Protein Cell. 11:549–564. 2020. View Article : Google Scholar : PubMed/NCBI

21 

Zhang G, Liu A, Yang Y, Xia Y, Li W, Liu Y, Zhang J, Cui Q, Wang D, Liu X, et al: Clinical predictive value of naïve and memory T cells in advanced NSCLC. Front Immunol. 13:9963482022. View Article : Google Scholar : PubMed/NCBI

22 

Reina-Campos M, Scharping NE and Goldrath AW: CD8+ T cell metabolism in infection and cancer. Nat Rev Immunol. 21:718–738. 2021. View Article : Google Scholar : PubMed/NCBI

23 

Wißfeld J, Werner A, Yan X, Ten Bosch N and Cui G: Metabolic regulation of immune responses to cancer. Cancer Biol Med. 19:1528–1542. 2022.PubMed/NCBI

24 

Ma S, Ming Y, Wu J and Cui G: Cellular metabolism regulates the differentiation and function of T-cell subsets. Cell Mol Immunol. 21:419–435. 2024. View Article : Google Scholar : PubMed/NCBI

25 

Araujo L, Khim P, Mkhikian H, Mortales CL and Demetriou M: Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation. Elife. 6:e213302017. View Article : Google Scholar : PubMed/NCBI

26 

Kumar A and Chamoto K: Immune metabolism in PD-1 blockade-based cancer immunotherapy. Int Immunol. 33:17–26. 2021. View Article : Google Scholar : PubMed/NCBI

27 

Li F, Liu H, Zhang D, Ma Y and Zhu B: Metabolic plasticity and regulation of T cell exhaustion. Immunology. 167:482–494. 2022. View Article : Google Scholar : PubMed/NCBI

28 

Upadhyay S, Khan S and Hassan MI: Exploring the diverse role of pyruvate kinase M2 in cancer: Navigating beyond glycolysis and the Warburg effect. Biochim Biophys Acta Rev Cancer. 1879:1890892024. View Article : Google Scholar : PubMed/NCBI

29 

Barba I, Carrillo-Bosch L and Seoane J: Targeting the Warburg effect in cancer: Where do we stand? Int J Mol Sci. 25:31422024. View Article : Google Scholar : PubMed/NCBI

30 

von Meyenn L, Bertschi NL and Schlapbach C: Targeting T cell metabolism in inflammatory skin disease. Front Immunol. 10:22852019. View Article : Google Scholar : PubMed/NCBI

31 

Zhang Z and Li X, Yang F, Chen C, Liu P, Ren Y, Sun P, Wang Z, You Y, Zeng YX and Li X: DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis. Nat Commun. 12:58722021. View Article : Google Scholar : PubMed/NCBI

32 

Gerriets VA, Kishton RJ, Nichols AG, Macintyre AN, Inoue M, Ilkayeva O, Winter PS, Liu X, Priyadharshini B, Slawinska ME, et al: Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest. 125:194–207. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Adeva-Andany MM, Pérez-Felpete N, Fernández-Fernández C, Donapetry-García C and Pazos-García C: Liver glucose metabolism in humans. Biosci Rep. 36:e004162016. View Article : Google Scholar : PubMed/NCBI

34 

Icard P, Alifano M, Donnadieu E and Simula L: Fructose-1,6-bisphosphate promotes PI3K and glycolysis in T cells? Trends Endocrinol Metab. 32:540–543. 2021. View Article : Google Scholar : PubMed/NCBI

35 

Bilanges B, Posor Y and Vanhaesebroeck B: PI3K isoforms in cell signalling and vesicle trafficking. Nat Rev Mol Cell Biol. 20:515–534. 2019. View Article : Google Scholar : PubMed/NCBI

36 

Shen Q, Han Y, Wu K, He Y, Jiang X, Liu P, Xia C, Xiong Q, Liu R, Chen Q, et al: MrgprF acts as a tumor suppressor in cutaneous melanoma by restraining PI3K/Akt signaling. Signal Transduct Target Ther. 7:1472022. View Article : Google Scholar : PubMed/NCBI

37 

Akhtar N and Jabeen I: Pharmacoinformatic approaches to design novel inhibitors of protein kinase B pathways in cancer. Curr Cancer Drug Targets. 18:830–846. 2018. View Article : Google Scholar : PubMed/NCBI

38 

Sun K, Luo J, Guo J, Yao X, Jing X and Guo F: The PI3K/AKT/mTOR signaling pathway in osteoarthritis: A narrative review. Osteoarthritis Cartilage. 28:400–409. 2020. View Article : Google Scholar : PubMed/NCBI

39 

Jhanwar-Uniyal M, Wainwright JV, Mohan AL, Tobias ME, Murali R, Gandhi CD and Schmidt MH: Diverse signaling mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a formidable relationship. Adv Biol Regul. 72:51–62. 2019. View Article : Google Scholar : PubMed/NCBI

40 

Chen Y and Zhou X: Research progress of mTOR inhibitors. Eur J Med Chem. 208:1128202020. View Article : Google Scholar : PubMed/NCBI

41 

Dwyer CJ, Arhontoulis DC, Rangel Rivera GO, Knochelmann HM, Smith AS, Wyatt MM, Rubinstein MP, Atkinson C, Thaxton JE, Neskey DM and Paulos CM: Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8+ T cells. Eur J Immunol. 50:1386–1399. 2020. View Article : Google Scholar : PubMed/NCBI

42 

Preite S, Gomez-Rodriguez J, Cannons JL and Schwartzberg PL: T and B-cell signaling in activated PI3K delta syndrome: From immunodeficiency to autoimmunity. Immunol Rev. 291:154–173. 2019. View Article : Google Scholar : PubMed/NCBI

43 

Chapman NM, Yoder AN, Barbón KM, Bilal MY, Connolly SF and Houtman JC: Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells. J Leukoc Biol. 97:285–296. 2015. View Article : Google Scholar : PubMed/NCBI

44 

Coppola C, Hopkins B, Huhn S, Du Z, Huang Z and Kelly WJ: Investigation of the Impact from IL-2, IL-7, and IL-15 on the growth and signaling of activated CD4+ T Cells. Int J Mol Sci. 21:78142020. View Article : Google Scholar : PubMed/NCBI

45 

Mossmann D, Park S and Hall MN: mTOR signalling and cellular metabolism are mutual determinants in cancer. Nat Rev Cancer. 18:744–757. 2018. View Article : Google Scholar : PubMed/NCBI

46 

Werlen G, Jain R and Jacinto E: MTOR signaling and metabolism in Early T cell development. Genes (Basel). 12:7282021. View Article : Google Scholar : PubMed/NCBI

47 

Wen L: The tumor immunotherapy effect of dendritic cells carrying anti CD40 single chain antibodies and the expression and role of CD40 on CD4+T cell surface D. Suzhou University; 2012

48 

Zappasodi R, Serganova I, Cohen IJ, Maeda M, Shindo M, Senbabaoglu Y, Watson MJ, Leftin A, Maniyar R, Verma S, et al: CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours. Nature. 591:652–658. 2021. View Article : Google Scholar : PubMed/NCBI

49 

Beckermann KE, Hongo R, Ye X, Young K, Carbonell K, Healey DCC, Siska PJ, Barone S, Roe CE, Smith CC, et al: CD28 costimulation drives tumor-infiltrating T cell glycolysis to promote inflammation. JCI Insight. 5:e1387292020. View Article : Google Scholar : PubMed/NCBI

50 

Sugiura D, Okazaki IM, Maeda TK, Maruhashi T, Shimizu K, Arakaki R, Takemoto T, Ishimaru N and Okazaki T: PD-1 agonism by anti-CD80 inhibits T cell activation and alleviates autoimmunity. Nat Immunol. 23:399–410. 2022. View Article : Google Scholar : PubMed/NCBI

51 

Sun C, Mezzadra R and Schumacher TN: Regulation and function of the PD-L1 checkpoint. Immunity. 48:434–452. 2018. View Article : Google Scholar : PubMed/NCBI

52 

Ribas A and Wolchok JD: Cancer immunotherapy using checkpoint blockade. Science. 359:1350–1355. 2018. View Article : Google Scholar : PubMed/NCBI

53 

Lin F, Chen Y, Huang B, Ruan S, Lin J, Chen Z, Huang C and Zhao B: Application of immune checkpoint inhibitors for resectable gastric/gastroesophageal cancer. Front Pharmacol. 15:13915622024. View Article : Google Scholar : PubMed/NCBI

54 

Oyewole-Said D, Konduri V, Vazquez-Perez J, Weldon SA, Levitt JM and Decker WK: Beyond T-cells: Functional characterization of CTLA-4 expression in immune and non-immune cell types. Front Immunol. 11:6080242020. View Article : Google Scholar : PubMed/NCBI

55 

Xia S, Chen Q and Niu B: CD28: A new drug target for immune disease. Curr Drug Targets. 21:589–598. 2020. View Article : Google Scholar : PubMed/NCBI

56 

Kumagai S, Koyama S, Itahashi K, Tanegashima T, Lin YT, Togashi Y, Kamada T, Irie T, Okumura G, Kono H, et al: Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer Cell. 40:201–218.e9. 2022. View Article : Google Scholar : PubMed/NCBI

57 

Palaskas NJ, Garcia JD, Shirazi R, Shin DS, Puig-Saus C, Braas D, Ribas A and Graeber TG: Global alteration of T-lymphocyte metabolism by PD-L1 checkpoint involves a block of de novo nucleoside phosphate synthesis. Cell Discov. 5:622019. View Article : Google Scholar : PubMed/NCBI

58 

Dong S, Guo X, Han F, He Z and Wang Y: Emerging role of natural products in cancer immunotherapy. Acta Pharm Sin B. 12:1163–1185. 2022. View Article : Google Scholar : PubMed/NCBI

59 

Pulanco MC, Madsen AT, Tanwar A, Corrigan DT and Zang X: Recent advancements in the B7/CD28 immune checkpoint families: New biology and clinical therapeutic strategies. Cell Mol Immunol. 20:694–713. 2023. View Article : Google Scholar : PubMed/NCBI

60 

Sharma P, Goswami S, Raychaudhuri D, Siddiqui BA, Singh P, Nagarajan A, Liu J, Subudhi SK, Poon C, Gant KL, et al: Immune checkpoint therapy-current perspectives and future directions. Cell. 186:1652–1669. 2023. View Article : Google Scholar : PubMed/NCBI

61 

Zhang J, Wei X, Zhang Q, Jiao X, Li K, Geng M, Cao Y, Wang D, Cheng J and Yang J: Fish uses CTLA-4 immune checkpoint to suppress mTORC1-Controlled T-cell glycolysis and immunity. J Immunol. 212:1113–1128. 2024. View Article : Google Scholar : PubMed/NCBI

62 

Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, et al: Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 381:2020–2031. 2019. View Article : Google Scholar : PubMed/NCBI

63 

VanderWalde A, Bellasea SL, Kendra KL, Khushalani NI, Campbell KM, Scumpia PO, Kuklinski LF, Collichio F, Sosman JA, Ikeguchi A, et al: Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: A randomized phase 2 trial. Nat Med. 29:2278–2285. 2023. View Article : Google Scholar : PubMed/NCBI

64 

Cascone T, Leung CH, Weissferdt A, Pataer A, Carter BW, Godoy MCB, Feldman H, William WN Jr, Xi Y, Basu S, et al: Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: The phase 2 platform NEOSTAR Trial. Nat Med. 29:593–604. 2023. View Article : Google Scholar : PubMed/NCBI

65 

Grimm MO, Esteban E, Barthélémy P, Schmidinger M, Busch J, Valderrama BP, Charnley N, Schmitz M, Schumacher U, Leucht K, et al: Tailored immunotherapy approach with nivolumab with or without nivolumab plus ipilimumab as immunotherapeutic boost in patients with metastatic renal cell carcinoma (TITAN-RCC): A multicentre, single-arm, phase 2 trial. Lancet Oncol. 24:1252–1265. 2023. View Article : Google Scholar : PubMed/NCBI

66 

Liu L, Cheng Y, Zhang Z, Li J, Geng Y, Li Q, Luo D, Liang L, Liu W, Hu J and Ouyang W: Study on the allosteric activation mechanism of SHP2 via elastic network models and neural relational inference molecular dynamics simulation. Phys Chem Chem Phys. 25:23588–23601. 2023. View Article : Google Scholar : PubMed/NCBI

67 

Ai L, Xu A and Xu J: Roles of PD-1/PD-L1 pathway: Signaling, cancer, and beyond. Adv Exp Med Biol. 1248:33–59. 2020. View Article : Google Scholar : PubMed/NCBI

68 

Guo YJ, Pan WW, Liu SB, Shen ZF, Xu Y and Hu LL: ERK/MAPK signalling pathway and tumorigenesis. Exp Ther Med. 19:1997–2007. 2020.PubMed/NCBI

69 

Quan Z, Yang Y, Zheng H, Zhan Y, Luo J, Ning Y and Fan S: Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer. J Cancer. 13:3434–3443. 2022. View Article : Google Scholar : PubMed/NCBI

70 

Huang Q, Wu X, Wang Z, Chen X, Wang L, Lu Y, Xiong D, Liu Q, Tian Y, Lin H, et al: The primordial differentiation of tumor-specific memory CD8+ T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes. Cell. 185:4049–4066.e25. 2022. View Article : Google Scholar : PubMed/NCBI

71 

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

72 

Karim S, Mirza Z, Chaudhary AG, Abuzenadah AM, Gari M and Al-Qahtani MH: Assessment of radiation induced therapeutic effect and cytotoxicity in cancer patients based on transcriptomic profiling. Int J Mol Sci. 17:2502016. View Article : Google Scholar : PubMed/NCBI

73 

Ascierto ML, McMiller TL, Berger AE, Danilova L, Anders RA, Netto GJ, Xu H, Pritchard TS, Fan J, Cheadle C, et al: The intratumoral balance between metabolic and immunologic gene expression is associated with Anti-PD-1 response in patients with renal cell carcinoma. Cancer Immunol Res. 4:726–733. 2016. View Article : Google Scholar : PubMed/NCBI

74 

Van Damme H, Dombrecht B, Kiss M, Roose H, Allen E, Van Overmeire E, Kancheva D, Martens L, Murgaski A, Bardet PMR, et al: Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy. J Immunother Cancer. 9:e0017492021. View Article : Google Scholar : PubMed/NCBI

75 

Zou Z, Tao T, Li H and Zhu X: mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges. Cell Biosci. 10:312020. View Article : Google Scholar : PubMed/NCBI

76 

Lim LM, Kung LF, Kuo MC, Huang AM and Kuo HT: Timing of mTORI usage and outcomes in kidney transplant recipients. Int J Med Sci. 18:1179–1184. 2021. View Article : Google Scholar : PubMed/NCBI

77 

Kumari A, Gesumaria L, Liu YJ, Hughitt VK, Zhang X, Ceribelli M, Wilson KM, Klumpp-Thomas C, Chen L, McKnight C, et al: mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer. JCI Insight. 8:e1566572023. View Article : Google Scholar : PubMed/NCBI

78 

Daenthanasanmak A, Lin Y, Zhang M, Bryant BR, Petrus MN, Bamford RN, Thomas CJ, Miljkovic MD, Conlon KC and Waldmann TA: Enhanced efficacy of JAK1 inhibitor with mTORC1/C2 targeting in smoldering/chronic adult T cell leukemia. Transl Oncol. 14:1009132021. View Article : Google Scholar : PubMed/NCBI

79 

Bai S, Taylor SE, Jamalruddin MA, McGonigal S, Grimley E, Yang D, Bernstein KA and Buckanovich RJ: Targeting therapeutic resistance and multinucleate giant cells in CCNE1-Amplified HR-Proficient ovarian cancer. Mol Cancer Ther. 21:1473–1484. 2022. View Article : Google Scholar : PubMed/NCBI

80 

Sawaki M, Muramatsu Y, Togo K and Iwata H: Real-world treatment patterns of subsequent therapy after palbociclib in patients with advanced breast cancer in Japan Breast. 70:1–7. 2023.PubMed/NCBI

81 

Qiu HY, Wang PF and Zhang M: A patent review of mTOR inhibitors for cancer therapy (2011–2020). Expert Opin Ther Pat. 31:965–975. 2021. View Article : Google Scholar : PubMed/NCBI

82 

Vidigal AC, de Lucena DD, Beyerstedt S and Rangel ÉB: A comprehensive update of the metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation. Expert Opin Drug Metab Toxicol. 19:405–427. 2023. View Article : Google Scholar : PubMed/NCBI

83 

Franzin R, Netti GS, Spadaccino F, Porta C, Gesualdo L, Stallone G, Castellano G and Ranieri E: The use of immune checkpoint inhibitors in oncology and the occurrence of AKI: Where do we stand? Front Immunol. 11:5742712020. View Article : Google Scholar : PubMed/NCBI

84 

Zhang Y and Zhang Z: The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 17:807–821. 2020. View Article : Google Scholar : PubMed/NCBI

85 

Catalano M, Iannone LF, Nesi G, Nobili S, Mini E and Roviello G: Immunotherapy-related biomarkers: Confirmations and uncertainties. Crit Rev Oncol Hematol. 192:1041352023. View Article : Google Scholar : PubMed/NCBI

86 

Al-Hussainy A, Adams J, Simmons J and Kennedy J: Immune checkpoint inhibitor associated diarrhoea. BMJ Case Rep. 17:e2590572024. View Article : Google Scholar : PubMed/NCBI

87 

Blum SM, Rouhani SJ and Sullivan RJ: Effects of immune-related adverse events (irAEs) and their treatment on antitumor immune responses. Immunol Rev. 318:167–178. 2023. View Article : Google Scholar : PubMed/NCBI

88 

Ma S, Lei J and Lai X: Modeling tumour heterogeneity of PD-L1 expression in tumour progression and adaptive therapy. J Math Biol. 86:382023. View Article : Google Scholar : PubMed/NCBI

89 

Yi M, Zheng X, Niu M, Zhu S, Ge H and Wu K: Combination strategies with PD-1/PD-L1 blockade: Current advances and future directions. Mol Cancer. 21:282022. View Article : Google Scholar : PubMed/NCBI

90 

Chen Z, Yue Z, Wang R, Yang K and Li S: Nanomaterials: A powerful tool for tumor immunotherapy. Front Immunol. 13:9794692022. View Article : Google Scholar : PubMed/NCBI

91 

Li J, Zeng H, Li L, Yang Q, He L and Dong M: Advanced generation therapeutics: Biomimetic nanodelivery system for tumor immunotherapy. ACS Nano. 17:24593–24618. 2023. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang S, Liu C, Yang C, Jin Y, Cui Q, Wang D, Ge T, He G, Li W, Zhang G, Zhang G, et al: PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review). Oncol Lett 28: 567, 2024.
APA
Wang, S., Liu, C., Yang, C., Jin, Y., Cui, Q., Wang, D. ... Yu, J. (2024). PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review). Oncology Letters, 28, 567. https://doi.org/10.3892/ol.2024.14700
MLA
Wang, S., Liu, C., Yang, C., Jin, Y., Cui, Q., Wang, D., Ge, T., He, G., Li, W., Zhang, G., Liu, A., Xia, Y., Liu, Y., Yu, J."PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review)". Oncology Letters 28.6 (2024): 567.
Chicago
Wang, S., Liu, C., Yang, C., Jin, Y., Cui, Q., Wang, D., Ge, T., He, G., Li, W., Zhang, G., Liu, A., Xia, Y., Liu, Y., Yu, J."PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review)". Oncology Letters 28, no. 6 (2024): 567. https://doi.org/10.3892/ol.2024.14700
Copy and paste a formatted citation
x
Spandidos Publications style
Wang S, Liu C, Yang C, Jin Y, Cui Q, Wang D, Ge T, He G, Li W, Zhang G, Zhang G, et al: PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review). Oncol Lett 28: 567, 2024.
APA
Wang, S., Liu, C., Yang, C., Jin, Y., Cui, Q., Wang, D. ... Yu, J. (2024). PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review). Oncology Letters, 28, 567. https://doi.org/10.3892/ol.2024.14700
MLA
Wang, S., Liu, C., Yang, C., Jin, Y., Cui, Q., Wang, D., Ge, T., He, G., Li, W., Zhang, G., Liu, A., Xia, Y., Liu, Y., Yu, J."PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review)". Oncology Letters 28.6 (2024): 567.
Chicago
Wang, S., Liu, C., Yang, C., Jin, Y., Cui, Q., Wang, D., Ge, T., He, G., Li, W., Zhang, G., Liu, A., Xia, Y., Liu, Y., Yu, J."PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review)". Oncology Letters 28, no. 6 (2024): 567. https://doi.org/10.3892/ol.2024.14700
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