Education, Science, Technology, Innovation and Life
Open Access
Sign In

Research Progress of Immune Checkpoint Inhibitors in Melanoma

Download as PDF

DOI: 10.23977/medsc.2023.040811 | Downloads: 11 | Views: 301


Xinyu Chang 1, Liwen Wang 2


1 Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China
2 Department of Dermatology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712000, China

Corresponding Author

Liwen Wang


Melanoma, also known as malignant melanoma, is a malignant tumor originating from melanocytes that is highly malignant, aggressive, and has a poor prognosis. Although melanoma accounts for about 10% of skin cancers, melanoma is the leading cause of death from skin cancers. Thus, it is essential to study the treatment of melanoma. Immunotherapy has produced durable clinical responses with long-term remissions in melanoma. In this article, we present a review of immune checkpoint inhibitors in melanoma treatment, and will introduce CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors.


Melanoma; immunotherapy; immune checkpoint; CTLA-4; PD-1; PD-L1


Xinyu Chang, Liwen Wang, Research Progress of Immune Checkpoint Inhibitors in Melanoma. MEDS Clinical Medicine (2023) Vol. 4: 73-79. DOI:


[1] Davis Lauren E, Shalin Sara C, Tackett Alan J, et al. Current state of melanoma diagnosis and treatment [J]. Cancer biology & therapy, 2019, 20(11):1366-1379.
[2] Schadendorf Dirk, Hodi F Stephen, Robert Caroline, et al. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma [J]. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 2015, 33(17):1889-1894.
[3] C. Lebbé, J.S. Weber, M. Maio, et al. Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies [J]. Annals of Oncology, 2014, 25(11):2277-2284.
[4] Meyers D E, Banerji S. Biomarkers of immune checkpoint inhibitor efficacy in cancer [J]. Current oncology (Toronto, Ont.), 2020, 27(2):S106-S114.
[5] Li Bin, Chan Ho Lam, Chen Pingping, et al. Immune Checkpoint Inhibitors: Basics and Challenges [J]. Current medicinal chemistry, 2019, 26(17):3009-3025.
[6] Lv Mengze, Chen Meixia, Zhang Rui, et al. Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy [J]. Cell research, 2020, 30(11):966-979.
[7] Zhao Yujie, Liu Xu, Liu Xinyu, et al. Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer [J]. Frontiers in Immunology, 2022, 13:955920-955920.
[8] Priyanka Khanna, Normand Blais, Pierre-Olivier Gaudreau, et al. Immunotherapy Comes of Age in Lung Cancer [J]. Clinical Lung Cancer, 2016, 18(1):13-22.
[9] Zhang Hao, Dai Ziyu, Wu Wantao, et al. Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer [J]. Journal of Experimental & Clinical Cancer Research, 2021, 40(1):184-184.
[10] Zhao Yinghao, Yang Wei, Huang Yuanyuan, et al. Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy [J]. Cellular Physiology and Biochemistry, 2018, 47(2):721-734.
[11] Rowshanravan Behzad, Halliday Neil, Sansom David M, et al. CTLA-4: a moving target in immunotherapy [J]. Blood, 2018, 131(1):58-67.
[12] Sharpe Arlene H, Abbas Abul K. T-cell costimulation--biology, therapeutic potential, and challenges [J]. The New England journal of medicine, 2006, 355(10):973-975.
[13] Carreno B M, Bennett F, Chau T A, et al. CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression [J]. Journal of immunology (Baltimore, Md.: 1950), 2000, 165(3):1352-1356.
[14] Wojtukiewicz Marek Z, Rek Magdalena M, Karpowicz Kamil, et al. Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners [J]. Cancer metastasis reviews, 2021, 40(3):1-34.
[15] Dalle Stéphane, Mortier Laurent, Corrie Pippa, et al. Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study [J]. BMC Cancer, 2021, 21(1):642-642.
[16] Larkin James, Chiarion-Sileni Vanna, Gonzalez Rene, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma [J]. The New England journal of medicine, 2019, 381(16):1535-1546.
[17] Ribas Antoni, Kefford Richard, Marshall Margaret A, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma [J]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013, 31(5):616-622.
[18] Bajor David L, Mick Rosemarie, Riese Matthew J, et al. Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma [J]. Oncoimmunology, 2018, 7(10):e1468956.
[19] Xuewu Zhang, Jean-Claude D. Schwartz, Xiaoling Guo, et al. Structural and Functional Analysis of the Costimulatory Receptor Programmed Death-1 [J]. Immunity, 2004, 20(3):337-347.
[20] Han Jiaqian, Xu Xiaobo, Liu Zi, et al. Recent advances of molecular mechanisms of regulating PD-L1 expression in melanoma [J]. International Immunopharmacology, 2020, 88:106971.
[21] Zhou Lijuan, Wen Liang, Sheng Youyu, et al. The PD-1/PD-L1 pathway in murine hair cycle transition: a potential anagen phase regulator[J]. Archives of Dermatological Research, 2021, 313(9):1-8.
[22] Hosseinzadeh Ramin, Feizisani Fahimeh, Shomali Navid, et al. PD-1/PD-L1 Blockade: Prospectives for immunotherapy in Cancer and Autoimmunity [J]. IUBMB life, 2021, 73(11):1293-1306.
[23] Brahmer Julie R, Drake Charles G, Wollner Ira, et al. Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates [J]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2023, 41(4):715-723.
[24] Larkin James, Minor David, D'Angelo Sandra, et al. Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial [J]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018, 36(4):383-390.
[25] Yamazaki Naoya, Takenouchi Tatsuya, Nakamura Yasuhiro, et al. Prospective observational study of the efficacy of nivolumab in Japanese patients with advanced melanoma (CREATIVE study) [J]. Japanese journal of clinical oncology, 2021, 51(8):1232-1241.
[26] Barone Amy, Hazarika Maitreyee, Theoret Marc R, et al. FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma [J]. Clinical cancer research : an official journal of the American Association for Cancer Research, 2017, 23(19):5661-5665.
[27] Bottomley Andrew, Coens Corneel, Mierzynska Justyna, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial [J]. The Lancet Oncology, 2021, 22(5):655-664.
[28] Shiravand Yavar, Khodadadi Faezeh, Kashani Seyyed Mohammad Amin, et al. Immune Checkpoint Inhibitors in Cancer Therapy [J]. Current Oncology, 2022, 29(5):3044-3060.
[29] Ribas Antoni, Algazi Alain, Ascierto Paolo A, et al. PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma [J]. Nature Communications, 2020, 11(1):6262-6262.
[30] Keilholz Ulrich, Mehnert Janice M, Bauer Sebastian, et al. Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial [J]. Journal for immunotherapy of cancer, 2019, 7(1):12.
[31] Bagchi Sreya, Yuan Robert, Engleman Edgar G, et al. Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance [J]. Annual review of pathology, 2020, 16: 223-249.
[32] Gomes Nuno, Sibaud Vincent, Azevedo Filomena, et al. Cutaneous Toxicity of Immune Checkpoint Inhibitors: A Narrative Review [J]. Acta medica portuguesa, 2020, 33(5):335-343.
[33] Horvat Troy Z, Adel Nelly G, Dang Thu-Oanh, et al. Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center [J]. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 2015, 33(28):3193-3198.
[34] Postow Michael A. Managing immune checkpoint-blocking antibody side effects [J]. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting, 2015:76-83.
[35] Wang Quanqiu, Xu Rong. Immunotherapy-related adverse events (irAEs): extraction from FDA drug labels and comparative analysis.[J]. JAMIA open, 2019, 2(1):173-178.
[36] Gide Tuba N, Pires da Silva Inês, Quek Camelia, et al. Clinical and Molecular Heterogeneity in Patients with Innate Resistance to Anti-PD-1 +/- Anti-CTLA-4 Immunotherapy in Metastatic Melanoma Reveals Distinct Therapeutic Targets [J]. Cancers, 2021, 13(13):3186-3186.
[37] Gide Tuba N, Wilmott James S, Scolyer Richard A, et al. Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Metastatic Melanoma [J]. Clinical cancer research: an official journal of the American Association for Cancer Research, 2018, 24(6):1260-1270.
[38] Kluger Harriet M, Tawbi Hussein A, Ascierto Maria L, et al. Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce [J]. Journal for immunotherapy of cancer, 2020, 8(1):e000398.
[39] Maria Letizia Motti, Michele Minopoli, Gioconda Di Carluccio, et al. MicroRNAs as Key Players in Melanoma Cell Resistance to MAPK and Immune Checkpoint Inhibitors [J]. International Journal of Molecular Sciences, 2020, 21(12):4544.
[40] Veronica Huber, Viviana Vallacchi, Viktor Fleming, et al. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma [J]. Journal of Clinical Investigation, 2018, 128(12):5505-5516.
[41] Cortez Maria Angelica, Anfossi Simone, Ramapriyan Rishab, et al. Role of miRNAs in immune responses and immunotherapy in cancer [J]. Genes, chromosomes & cancer, 2019, 58(4):244-253.

Downloads: 4795
Visits: 209418

Sponsors, Associates, and Links

All published work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2016 - 2031 Clausius Scientific Press Inc. All Rights Reserved.