Immunotherapy and Immune Checkpoints: Unlocking The Immune System’s Potential to Treat Cancer
DOI:
https://doi.org/10.37304/jkupr.v13i2.21738Keywords:
Immunotherapy, immune checkpoint, cancerAbstract
Conventional cancer therapies, such as surgery, chemotherapy, and radiation therapy, often produce limited results and negatively affect patients' quality of life. In recent years, immunotherapy based on immune checkpoint inhibitors (ICIs) has emerged as a promising new approach. Immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, play a crucial role in suppressing the immune response to tumors, making them primary targets in ICI therapy. This study examines the mechanisms of immune checkpoints, the efficacy of ICI therapy, and the remaining challenges in clinical practice. The review was conducted through a literature review of scientific publications and the latest clinical trial results. The results demonstrate the efficacy of ICIs, such as ipilimumab and pembrolizumab, in improving overall and progression-free survival rates across various types of cancer, particularly melanoma and non-small cell lung cancer. Combining two ICIs has been shown to have higher synergistic effects than monotherapy, as demonstrated in the CheckMate 067 and KEYNOTE-024 clinical trials. Despite its promise, this therapy is not fully effective in all patients due to immune resistance, autoimmune side effects, and the complexity of tumor heterogeneity and the immune microenvironment. Therefore, combination therapy strategies, dose adjustments, schedule modifications, and personalized approaches based on biomarkers are needed to optimize clinical benefits and expand the scope of therapy. In conclusion, ICIs hold great potential for future cancer therapies and are being developed to be more effective and personalized.
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Mejía-Guarnizo LV, Monroy-Camacho PS, Turizo-Smith AD, Rodríguez-García JA.(2023). The role of immune checkpoints in antitumor response: a potential antitumor immunotherapy. Front Immunol, doi: 10.3389/fimmu.2023. 1298 571/full
Meng L, Wu H, Wu J, Ding P, He J, Sang M, et al. (2024). Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks. Cell Death Dis, 15(1). doi: 10.1038/s41419-023-063 89-5
Yin Q, Wu L, Han L, Zheng X, Tong R, Li L, et al. (2023). Immune-related adverse events of immune checkpoint inhibitors: a review. Front Immunol, 25(14). doi: 10.3389/fimmu. 2023.11 67975/full
Das CK, Singh SK. (2022). Immune Checkpoint Inhibitors in Cancer Therapy: A Ray of Hope. In: Biomedical Translational Research, 29(5): 393–411. doi: 10.1007/978-981-16-8845-4_20
Bagchi S, Yuan R, Engleman EG. (2021). Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance. Annu Rev Pathol Mech Dis, 16(1):223–49. doi: 10.1146/annurev-pathol-042020-042741
Lao Y, Shen D, Zhang W, He R, Jiang M. (2022). Immune Checkpoint Inhibitors in Cancer Therapy—How to Overcome Drug Resistance? Cancers (Basel), 14(15):3575. doi: 10.3390/ cancers14153575
Mo D-C, Huang J-F, Luo P-H, Huang S-X, Wang H-L. (2021). The efficacy and safety of combination therapy with immune checkpoint inhibitors in non-small cell lung cancer: A meta-analysis. Int Immunopharmacol, 96:107594. doi: 10.1016/j.intimp.2021.107594
Kong X, Zhang J, Chen S, Wang X, Xi Q, Shen H, et al. (2024). Immune checkpoint inhibitors: breakthroughs in cancer treatment. Cancer Biol Med, 21(6);1–11. doi: 10.20892/j.issn.2095-3941.2024.0055
Zhang H, Dai Z, Wu W, Wang Z, Zhang N, Zhang L, et al. (2021). Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer. J Exp Clin Cancer Res, 40(1):184. doi: 10.1186/s13046-021-01987-7
Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, Chumsri S, Lou Y. (2018). Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol, 11(1):39. doi: 10.1186/s13045-018-0582-8
Shiravand Y, Khodadadi F, Kashani SMA, Hosseini-Fard SR, Hosseini S, Sadeghirad H, et al. (2022). Immune Checkpoint Inhibitors in Cancer Therapy. Curr Oncol, 29(5):3044–60. doi: 10.3390/curroncol29050247.
He X, Xu C. (2020). Immune checkpoint signaling and cancer immunotherapy. Cell Res, 30(8):660–9. doi: 10.1038/s41422-020-0343-4
Rezazadeh‐Gavgani E, Majidazar R, Lotfinejad P, Kazemi T, Shamekh A. (2025). Immune Checkpoint Molecules: A Review on Pathways and Immunotherapy Implications. Immunity, Inflamm Dis, 13(4). doi: 10.1002/iid3.70196
Sobhani N, Tardiel-Cyril DR, Davtyan A, Generali D, Roudi R, Li Y. (2021). CTLA-4 in Regulatory T Cells for Cancer Immunotherapy. Cancers (Basel),13(6):1440. doi: 0.3390/cancers 13061440
Jiang Y, Chen M, Nie H, Yuan Y. (2019). PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations. Hum Vaccin Immunother, 15(5):1111–22. doi: 10.1080/21645515.2019.1571892
Beenen AC, Sauerer T, Schaft N, Dörrie J. 2022. Beyond Cancer: Regulation and Function of PD-L1 in Health and Immune-Related Diseases. Int J Mol Sci, 23(15):8599. doi: 10.3390/ijms 23158599
Hudson K, Cross N, Jordan-Mahy N, Leyland R. (2020). The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: Implications for Immunotherapy Treatment. Front Immunol, 21(11). doi: 10.3389/fimmu.2020.568931/full
Sauer N, Janicka N, Szlasa W, Skinderowicz B, Kołodzińska K, Dwernicka W, et al. (2018). TIM-3 as a promising target for cancer immunotherapy in a wide range of tumors. Cancer Immunol Immunother [Internet]. 2023 Nov 11;72(11):3405–25. Available from: https://link.springer.com/10.1007/s00262-023-03516-1
Naran K, Nundalall T, Chetty S, Barth S. (2018). Principles of Immunotherapy: Implications for Treatment Strategies in Cancer and Infectious Diseases. Front Microbiol, 21(9). doi: 10.3389/fmicb.2018.03158/full
Abdou Y, Pandey M, Sarma M, Shah S, Baron J, Ernstoff MS. (2020). Mechanism‐based treatment of cancer with immune checkpoint inhibitor therapies. Br J Clin Pharmacol, 86(9):1690–702. doi: 10.1111/bcp.14316
Marei HE, Hasan A, Pozzoli G, Cenciarelli C. (2023). Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired. Cancer Cell Int, 23(1):64. doi: 10.1186/s12935-023-029 02-0
Evans ST, Jani Y, Jansen CS, Yildirim A, Kalemoglu E, Bilen MA. (2024). Understanding and overcoming resistance to immunotherapy in genitourinary cancers. Cancer Biol Ther, 31;25(1). Available from: https://www.tandfonline.com/doi/full/10.1080/15384047.2024.2342599
Willsmore ZN, Coumbe BGT, Crescioli S, Reci S, Gupta A, Harris RJ, et al. (2021). Combined anti‐PD‐1 and anti‐CTLA‐4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action. Eur J Immunol. 51(3):544–56. doi: 10.1002/eji.202048747
Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature, 545(7652):60–5. doi: 10.1038/nature22079.
Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob J-J, Rutkowski P, Cowey CL, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol, 19(11):1480–92. doi: 10.1007/s00262-023-03516-1
Younis A, Gribben J. (2024). Immune Checkpoint Inhibitors: Fundamental Mechanisms, Current Status and Future Directions. Immuno, 4(3):186–210. doi: 10.3390/immuno403001
Long G V, Atkinson V, Cebon JS, Jameson MB, Fitzharris BM, McNeil CM, et al. (2017). Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (Keynote-029): an open-label, phase 1b trial. Lancet Oncol,. (9):1202–10. doi: 10.1016/S1470-2045(17)30428-X.
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