Published in:

Open Access 01-06-2025 | Checkpoint Inhibitors | MINI REVIEW

Lessons learned from a decade of immune checkpoint inhibition: The good, the bad, and the ugly

Authors: Jacob J. Adashek, Jillian A. Moran, Dung T. Le, Razelle Kurzrock

Published in: Cancer and Metastasis Reviews | Issue 2/2025

Abstract

Discovering the brakes/checkpoints that cancer places on the immune system to prevent being eradicated led to the 2018 Nobel Prize and the development of multiple Food and Drug Administration-approved immune checkpoint inhibitors (ICIs). ICIs have transformed the treatment of numerous cancer types and, remarkably, some patients with end-stage metastatic disease can achieve durable, complete remissions — cures. Still, ICIs cause significant immune-related toxicities, and most tumors are resistant. Unusual progression patterns such as pseudo-progression and hyper-progression (accelerated progression) can occur. Biomarkers for ICI response/resistance include microsatellite instability, high tumor mutational burden, and PD-L1 immunohistochemistry positivity; but they are imperfect, perhaps because of immune system complexity. Herein, we explore the good, the bad, and the ugly of ICIs in cancer treatment.

https://www.nobelprize.org/prizes/medicine/2018/press-release/

Buchbinder, E. I., & Desai, A. (2016). CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. American Journal Of Clinical Oncology, 39(1), 98–106. https://doi.org/10.1097/COC.0000000000000239CrossRefPubMedPubMedCentral

Lu, L., Zhan, M., Li, X. Y., Zhang, H., Dauphars, D. J., Jiang, J., Yin, H., Li, S. Y., Luo, S., Li, Y., & He, Y. W. (2022). Clinically approved combination immunotherapy: Current status, limitations, and future perspective. Curr Res Immunol, 3, 118–127. https://doi.org/10.1016/j.crimmu.2022.05.003CrossRefPubMedPubMedCentral

Mittendorf, E. A., Burgers, F., Haanen, J., & Cascone, T. (2022). Neoadjuvant immunotherapy: Leveraging the immune system to treat early-stage disease. American Society of Clinical Oncology Educational Book, 42, 1–15. https://doi.org/10.1200/EDBK_349411CrossRefPubMed

Jin, Y., Wei, J., Weng, Y., Feng, J., Xu, Z., Wang, P., Cui, X., Chen, X., Wang, J., & Peng, M. (2022). Adjuvant therapy with PD1/PDL1 inhibitors for human cancers: A systematic review and meta-analysis. Frontiers In Oncology, 12, 732814. https://doi.org/10.3389/fonc.2022.732814CrossRefPubMedPubMedCentral

Cercek, A., Lumish, M., Sinopoli, J., Weiss, J., Shia, J., Lamendola-Essel, M., El Dika, I. H., Segal, N., Shcherba, M., Sugarman, R., Stadler, Z., Yaeger, R., Smith, J. J., Rousseau, B., Argiles, G., Patel, M., Desai, A., Saltz, L. B., Widmar, M., … Diaz, L. A., Jr. (2022). PD-1 Blockade in mismatch repair-deficient, locally advanced rectal cancer. New England Journal Of Medicine, 386(25), 2363–2376. https://doi.org/10.1056/NEJMoa2201445CrossRefPubMed

Goodman, A. M., Piccioni, D., Kato, S., Boichard, A., Wang, H. Y., Frampton, G., Lippman, S. M., Connelly, C., Fabrizio, D., Miller, V., Sicklick, J. K., & Kurzrock, R. (2018). Prevalence of PDL1 amplification and preliminary response to immune checkpoint blockade in solid tumors. JAMA Oncology, 4(9), 1237–1244. https://doi.org/10.1001/jamaoncol.2018.1701CrossRefPubMedPubMedCentral

Goodman, A. M., Kato, S., Bazhenova, L., Patel, S. P., Frampton, G. M., Miller, V., Stephens, P. J., Daniels, G. A., & Kurzrock, R. (2017). Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Molecular Cancer Therapeutics, 16(11), 2598–2608. https://doi.org/10.1158/1535-7163.MCT-17-0386CrossRefPubMedPubMedCentral

Patel, S. P., & Kurzrock, R. (2015). PD-L1 Expression as a predictive biomarker in cancer immunotherapy. Molecular Cancer Therapeutics, 14(4), 847–856. https://doi.org/10.1158/1535-7163.MCT-14-0983CrossRefPubMed

10.

Bevins, N. J., Okamura, R., Montesion, M., Adashek, J. J., Goodman, A. M., & Kurzrock, R. (2022). Tumor infiltrating lymphocyte expression of PD-1 predicts response to anti-PD-1/PD-L1 immunotherapy. J Immunother Precis Oncol, 5(4), 90–97. https://doi.org/10.36401/JIPO-22-9

11.

Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., Leming, P. D., Spigel, D. R., Antonia, S. J., Horn, L., Drake, C. G., Pardoll, D. M., Chen, L., Sharfman, W. H., Anders, R. A., … Sznol, M. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New England Journal Of Medicine, 366(26), 2443–2454. https://doi.org/10.1056/NEJMoa1200690CrossRefPubMed

12.

Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., Wong, F., Azad, N. S., Rucki, A. A., Laheru, D., Donehower, R., Zaheer, A., Fisher, G. A., Crocenzi, T. S., Lee, J. J., … Diaz, L. A., Jr. (2017). Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science, 357(6349), 409–413. https://doi.org/10.1126/science.aan6733CrossRefPubMedPubMedCentral

13.

Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., Biedrzycki, B., Donehower, R. C., Zaheer, A., Fisher, G. A., Crocenzi, T. S., Lee, J. J., Duffy, S. M., Goldberg, R. M., de la Chapelle, A., … Diaz, L. A., Jr. (2015). PD-1 Blockade in tumors with mismatch-repair deficiency. New England Journal Of Medicine, 372(26), 2509–2520. https://doi.org/10.1056/NEJMoa1500596CrossRefPubMed

14.

Jardim, D. L., Goodman, A., de Melo Gagliato, D., & Kurzrock, R. (2021). The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell, 39(2), 154–173. https://doi.org/10.1016/j.ccell.2020.10.001CrossRefPubMed

15.

Thompson, J. A., Schneider, B. J., Brahmer, J., Achufusi, A., Armand, P., Berkenstock, M. K., Bhatia, S., Budde, L. E., Chokshi, S., Davies, M., Elshoury, A., Gesthalter, Y., Hegde, A., Jain, M., Kaffenberger, B. H., Lechner, M. G., Li, T., Marr, A., McGettigan, S., McPherson, J., Medina, T., Mohindra, N. A., Olszanski, A. J., Oluwole, O., Patel, S. P., Patil, P., Reddy, S., Ryder, M., Santomasso, B., Shofer, S., Sosman, J. A., Wang, Y., Zaha, V. G., Lyons, M., Dwyer, M., & Hang, L. (2022). Management of immunotherapy-related toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology. Journal Of The National Comprehensive Cancer Network, 20(4), 387–405. https://doi.org/10.6004/jnccn.2022.0020

16.

Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Rutkowski, P., Lao, C. D., Cowey, C. L., Schadendorf, D., Wagstaff, J., Dummer, R., Ferrucci, P. F., Smylie, M., Hogg, D., Hill, A., Marquez-Rodas, I., Haanen, J., Guidoboni, M., Maio, M., Schoffski, P., … Wolchok, J. D. (2019). Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. New England Journal Of Medicine, 381(16), 1535–1546. https://doi.org/10.1056/NEJMoa1910836CrossRefPubMed

17.

Petrelli, F., Signorelli, D., Ghidini, M., Ghidini, A., Pizzutilo, E. G., Ruggieri, L., Cabiddu, M., Borgonovo, K., Dognini, G., Brighenti, M., De Toma, A., Rijavec, E., Garassino, M. C., Grossi, F., & Tomasello, G. (2020). Association of steroids use with survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis. Cancers (Basel), 12(3). https://doi.org/10.3390/cancers12030546

18.

Renner, A., Burotto, M., & Rojas, C. (2019). Immune checkpoint inhibitor dosing: Can we go lower without compromising clinical efficacy? J Glob Oncol, 5, 1–5. https://doi.org/10.1200/JGO.19.00142CrossRefPubMed

19.

Champiat, S., Dercle, L., Ammari, S., Massard, C., Hollebecque, A., Postel-Vinay, S., Chaput, N., Eggermont, A., Marabelle, A., Soria, J. C., & Ferte, C. (2017). Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clinical Cancer Research, 23(8), 1920–1928. https://doi.org/10.1158/1078-0432.CCR-16-1741CrossRefPubMed

20.

Kato, S., Goodman, A., Walavalkar, V., Barkauskas, D. A., Sharabi, A., & Kurzrock, R. (2017). Hyperprogressors after immunotherapy: Analysis of genomic alterations associated with accelerated growth rate. Clinical Cancer Research, 23(15), 4242–4250. https://doi.org/10.1158/1078-0432.CCR-16-3133CrossRefPubMedPubMedCentral

21.

Adashek, J. J., Subbiah, I. M., Matos, I., Garralda, E., Menta, A. K., Ganeshan, D. M., & Subbiah, V. (2020). Hyperprogression and immunotherapy: Fact, fiction, or alternative fact? Trends Cancer, 6(3), 181–191. https://doi.org/10.1016/j.trecan.2020.01.005CrossRefPubMedPubMedCentral

22.

Adashek, J. J., Kato, S., Ferrara, R., Lo Russo, G., & Kurzrock, R. (2020). Hyperprogression and immune checkpoint inhibitors: Hype or progress? The Oncologist, 25(2), 94–98. https://doi.org/10.1634/theoncologist.2019-0636CrossRefPubMed

23.

Wolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Rutkowski, P., Lao, C. D., Cowey, C. L., Schadendorf, D., Wagstaff, J., Dummer, R., Ferrucci, P. F., Smylie, M., Butler, M. O., Hill, A., Marquez-Rodas, I., Haanen, J., Guidoboni, M., Maio, M., Schoffski, P., … Hodi, F. S. (2022). Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. Journal Of Clinical Oncology, 40(2), 127–137. https://doi.org/10.1200/JCO.21.02229CrossRefPubMed

24.

Motzer, R. J., McDermott, D. F., Escudier, B., Burotto, M., Choueiri, T. K., Hammers, H. J., Barthelemy, P., Plimack, E. R., Porta, C., George, S., Powles, T., Donskov, F., Gurney, H., Kollmannsberger, C. K., Grimm, M. O., Barrios, C., Tomita, Y., Castellano, D., Grunwald, V., … Tannir, N. M. (2022). Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer, 128(11), 2085–2097. https://doi.org/10.1002/cncr.34180CrossRefPubMed

25.

Brahmer, J. R., Lee, J. S., Ciuleanu, T. E., Bernabe Caro, R., Nishio, M., Urban, L., Audigier-Valette, C., Lupinacci, L., Sangha, R., Pluzanski, A., Burgers, J., Mahave, M., Ahmed, S., Schoenfeld, A. J., Paz-Ares, L. G., Reck, M., Borghaei, H., O’Byrne, K. J., Gupta, R. G., … Ramalingam, S. S. (2023). Five-year survival outcomes with nivolumab plus ipilimumab versus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer in CheckMate 227. Journal Of Clinical Oncology, 41(6), 1200–1212. https://doi.org/10.1200/JCO.22.01503CrossRefPubMed

26.

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication

27.

Andre, T., Berton, D., Curigliano, G., Sabatier, R., Tinker, A. V., Oaknin, A., Ellard, S., de Braud, F., Arkenau, H. T., Trigo, J., Gravina, A., Kristeleit, R., Moreno, V., Abdeddaim, C., Vano, Y. A., Samouelian, V., Miller, R., Boni, V., Torres, A. A., … Banerjee, S. (2023). Antitumor activity and safety of dostarlimab monotherapy in patients with mismatch repair deficient solid tumors: A nonrandomized controlled trial. JAMA Network Open, 6(11), e2341165. https://doi.org/10.1001/jamanetworkopen.2023.41165CrossRefPubMedPubMedCentral

28.

Wang, P., Chen, Y., & Wang, C. (2021). Beyond tumor mutation burden: Tumor neoantigen burden as a biomarker for immunotherapy and other types of therapy. Frontiers in Oncology, 11, 672677. https://doi.org/10.3389/fonc.2021.672677CrossRefPubMedPubMedCentral

29.

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors#:~:text=On%20June%2016%2C%202020%2C%20the

30.

Friedman, C. F., Hainsworth, J. D., Kurzrock, R., Spigel, D. R., Burris, H. A., Sweeney, C. J., Meric-Bernstam, F., Wang, Y., Levy, J., Grindheim, J., Shames, D. S., Schulze, K., Patel, A., & Swanton, C. (2022). Atezolizumab treatment of tumors with high tumor mutational burden from MyPathway, a multicenter, open-label, phase IIa multiple basket study. Cancer Discovery, 12(3), 654–669. https://doi.org/10.1158/2159-8290.CD-21-0450CrossRefPubMedPubMedCentral

31.

Cook, S., Samuel, V., Meyers, D. E., Stukalin, I., Litt, I., Sangha, R., Morris, D. G., Heng, D. Y. C., Pabani, A., Dean, M., & Navani, V. (2024). Immune-related adverse events and survival among patients with metastatic NSCLC treated with immune checkpoint inhibitors. JAMA Network Open, 7(1), e2352302. https://doi.org/10.1001/jamanetworkopen.2023.52302CrossRefPubMedPubMedCentral

32.

Pinato, D. J., Marron, T. U., Mishra-Kalyani, P. S., Gong, Y., Wei, G., Szafron, D., Sharon, E., Saeed, A., Jun, T., Dharmapuri, S., Naqash, A. R., Peeraphatdit, T., Gampa, A., Wang, Y., Khan, U., Muzaffar, M., Navaid, M., Lee, C. J., Lee, P. C., … Pelosof, L. (2021). Treatment-related toxicity and improved outcome from immunotherapy in hepatocellular cancer: Evidence from an FDA pooled analysis of landmark clinical trials with validation from routine practice. European Journal Of Cancer, 157, 140–152. https://doi.org/10.1016/j.ejca.2021.08.020CrossRefPubMed

33.

Schneider, B. J., Naidoo, J., Santomasso, B. D., Lacchetti, C., Adkins, S., Anadkat, M., Atkins, M. B., Brassil, K. J., Caterino, J. M., Chau, I., Davies, M. J., Ernstoff, M. S., Fecher, L., Ghosh, M., Jaiyesimi, I., Mammen, J. S., Naing, A., Nastoupil, L. J., Phillips, T., … Bollin, K. (2021). Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. Journal Of Clinical Oncology, 39(36), 4073–4126. https://doi.org/10.1200/JCO.21.01440CrossRefPubMed

34.

Amjad, M. T., Chidharla, A., & Kasi, A. (2024). Cancer chemotherapy. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Anusha Chidharla declares no relevant financial relationships with ineligible companies. Anup Kasi declares no relevant financial relationships with ineligible companies. https://www.ncbi.nlm.nih.gov/books/NBK564367/

35.

Centanni, M., Moes, D., Troconiz, I. F., Ciccolini, J., & van Hasselt, J. G. C. (2019). Clinical pharmacokinetics and pharmacodynamics of immune checkpoint inhibitors. Clinical Pharmacokinetics, 58(7), 835–857. https://doi.org/10.1007/s40262-019-00748-2CrossRefPubMedPubMedCentral

36.

Kanesvaran, R., Cordoba, R., & Maggiore, R. (2018). Immunotherapy in older adults with advanced cancers: Implications for clinical decision-making and future research. American Society of Clinical Oncology Educational Book, 38, 400–414. https://doi.org/10.1200/EDBK_201435CrossRefPubMed

37.

Schaft, N., Dorrie, J., Schuler, G., Schuler-Thurner, B., Sallam, H., Klein, S., Eisenberg, G., Frankenburg, S., Lotem, M., & Khatib, A. (2023). The future of affordable cancer immunotherapy. Frontiers In Immunology, 14, 1248867. https://doi.org/10.3389/fimmu.2023.1248867CrossRefPubMedPubMedCentral

38.

Shin, Y. E., Kumar, A., & Guo, J. J. (2023). Spending, utilization, and price trends for immune checkpoint inhibitors in US Medicaid Programs: An empirical analysis from 2011 to 2021. Clinical Drug Investigation, 43(4), 289–298. https://doi.org/10.1007/s40261-023-01254-xCrossRefPubMedPubMedCentral

39.

Adashek, J. J., Kato, S., Nishizaki, D., Miyashita, H., De, P., Lee, S., Pabla, S., Nesline, M., Conroy, J. M., DePietro, P., Lippman, S., & Kurzrock, R. (2023). LAG-3 transcriptomic expression patterns across malignancies: Implications for precision immunotherapeutics. Cancer Medicine, 12(12), 13155–13166. https://doi.org/10.1002/cam4.6000CrossRefPubMedPubMedCentral

40.

Sakaguchi, T., Yoshino, H., Yonemori, M., Miyamoto, K., Sugita, S., Matsushita, R., Itesako, T., Tatarano, S., Nakagawa, M., & Enokida, H. (2018). Regulation of ITGA3 by the dual-stranded microRNA-199 family as a potential prognostic marker in bladder cancer. British Journal Of Cancer, 118(6), e7. https://doi.org/10.1038/bjc.2017.439CrossRefPubMedPubMedCentral

41.

Krishnamurthy, N., Goodman, A. M., Barkauskas, D. A., & Kurzrock, R. (2021). STK11 alterations in the pan-cancer setting: Prognostic and therapeutic implications. European Journal Of Cancer, 148, 215–229. https://doi.org/10.1016/j.ejca.2021.01.050CrossRefPubMedPubMedCentral

42.

Cortes, J., Rugo, H. S., Cescon, D. W., Im, S. A., Yusof, M. M., Gallardo, C., Lipatov, O., Barrios, C. H., Perez-Garcia, J., Iwata, H., Masuda, N., Torregroza Otero, M., Gokmen, E., Loi, S., Guo, Z., Zhou, X., Karantza, V., Pan, W., Schmid, P., & Investigators, K. (2022). Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. New England Journal Of Medicine, 387(3), 217–226. https://doi.org/10.1056/NEJMoa2202809CrossRefPubMed

43.

Gogishvili, M., Melkadze, T., Makharadze, T., Giorgadze, D., Dvorkin, M., Penkov, K., Laktionov, K., Nemsadze, G., Nechaeva, M., Rozhkova, I., Kalinka, E., Gessner, C., Moreno-Jaime, B., Passalacqua, R., Li, S., McGuire, K., Kaul, M., Paccaly, A., Quek, R. G. W., … Rietschel, P. (2022). Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: A randomized, controlled, double-blind phase 3 trial. Nature Medicine, 28(11), 2374–2380. https://doi.org/10.1038/s41591-022-01977-yCrossRefPubMedPubMedCentral

44.

Mok, T. S. K., Wu, Y. L., Kudaba, I., Kowalski, D. M., Cho, B. C., Turna, H. Z., Castro, G., Jr., Srimuninnimit, V., Laktionov, K. K., Bondarenko, I., Kubota, K., Lubiniecki, G. M., Zhang, J., Kush, D., Lopes, G., & Investigators, K. (2019). Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial. Lancet, 393(10183), 1819–1830. https://doi.org/10.1016/S0140-6736(18)32409-7CrossRefPubMed

45.

https://www.fda.gov/drugs/fda-expands-pembrolizumab-indication-first-line-treatment-nsclc-tps-1

46.

Del Rivero, J., Cordes, L. M., Klubo-Gwiezdzinska, J., Madan, R. A., Nieman, L. K., & Gulley, J. L. (2020). Endocrine-related adverse events related to immune checkpoint inhibitors: Proposed algorithms for management. The Oncologist, 25(4), 290–300. https://doi.org/10.1634/theoncologist.2018-0470CrossRefPubMed

47.

Kim, H., Lee, J. E., Hong, S. H., Lee, M. A., Kang, J. H., & Kim, I. H. (2019). The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: A retrospective study. BMC Cancer, 19(1), 1100. https://doi.org/10.1186/s12885-019-6267-zCrossRefPubMedPubMedCentral

48.

Bjork, J. R., Bolte, L. A., Maltez Thomas, A., Lee, K. A., Rossi, N., Wind, T. T., Smit, L. M., Armanini, F., Asnicar, F., Blanco-Miguez, A., Board, R., Calbet-Llopart, N., Derosa, L., Dhomen, N., Brooks, K., Harland, M., Harries, M., Lorigan, P., Manghi, P., … Weersma, R. K. (2024). Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma. Nature Medicine, 30(3), 785–796. https://doi.org/10.1038/s41591-024-02803-3CrossRefPubMedPubMedCentral

49.

Lopes, S., Pabst, L., Dory, A., Klotz, M., Gourieux, B., Michel, B., & Mascaux, C. (2023). Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis. Frontiers In Immunology, 14, 1070076. https://doi.org/10.3389/fimmu.2023.1070076CrossRefPubMed

50.

Medjebar, S., Truntzer, C., Perrichet, A., Limagne, E., Fumet, J. D., Richard, C., Elkrief, A., Routy, B., Rebe, C., & Ghiringhelli, F. (2020). Angiotensin-converting enzyme (ACE) inhibitor prescription affects non-small-cell lung cancer (NSCLC) patients response to PD-1/PD-L1 immune checkpoint blockers. Oncoimmunology, 9(1), 1836766. https://doi.org/10.1080/2162402X.2020.1836766CrossRefPubMedPubMedCentral

51.

Wang, D. Y., Salem, J. E., Cohen, J. V., Chandra, S., Menzer, C., Ye, F., Zhao, S., Das, S., Beckermann, K. E., Ha, L., Rathmell, W. K., Ancell, K. K., Balko, J. M., Bowman, C., Davis, E. J., Chism, D. D., Horn, L., Long, G. V., Carlino, M. S., … Johnson, D. B. (2018). Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis. JAMA Oncology, 4(12), 1721–1728. https://doi.org/10.1001/jamaoncol.2018.3923CrossRefPubMedPubMedCentral

52.

Rajan A, Sivapiromrat AK, McAdams MJ (2024) Immunotherapy for thymomas and thymic carcinomas: Current status and future directions. Cancers (Basel) 16 (7). https://doi.org/10.3390/cancers16071369

53.

Singavi, A. K., Kilari, S. M. D., Alqwasmi, A., Ritch, P. S., Thomas, J. P., Martin, A. L., Oxencis, C., Ali, S., & George, B. (2017). Predictive biomarkers for hyper-progression (HP) in response to immune checkpoint inhibitors (ICI) – Analysis of somatic alterations (SAs). Annals of Oncology 28 (suppl_5) c. J Annals of Oncology. https://doi.org/10.1093/annonc/mdx376.006%

54.

Kamada, T., Togashi, Y., Tay, C., Ha, D., Sasaki, A., Nakamura, Y., Sato, E., Fukuoka, S., Tada, Y., Tanaka, A., Morikawa, H., Kawazoe, A., Kinoshita, T., Shitara, K., Sakaguchi, S., & Nishikawa, H. (2019). PD-1(+) regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.1822001116CrossRefPubMedPubMedCentral

55.

Ma, Y., Wang, Q., Dong, Q., Zhan, L., & Zhang, J. (2019). How to differentiate pseudoprogression from true progression in cancer patients treated with immunotherapy. American Journal of Cancer Research, 9(8), 1546–1553.PubMedPubMedCentral

56.

Jensen, T. J., Goodman, A. M., Kato, S., Ellison, C. K., Daniels, G. A., Kim, L., Nakashe, P., McCarthy, E., Mazloom, A. R., McLennan, G., Grosu, D. S., Ehrich, M., & Kurzrock, R. (2019). Genome-wide sequencing of cell-free DNA identifies copy-number alterations that can be used for monitoring response to immunotherapy in cancer patients. Molecular Cancer Therapeutics, 18(2), 448–458. https://doi.org/10.1158/1535-7163.MCT-18-0535CrossRefPubMed

57.

Blank, C. U., Lucas, M. W., Scolyer, R. A., van de Wiel, B. A., Menzies, A. M., Lopez-Yurda, M., Hoeijmakers, L. L., Saw, R. P. M., Lijnsvelt, J. M., Maher, N. G., Pulleman, S. M., Gonzalez, M., Torres Acosta, A., van Houdt, W. J., Lo, S. N., Kuijpers, A. M. J., Spillane, A., Klop, W. M. C., Pennington, T. E., … Long, G. V. (2024). Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma. New England Journal of Medicine, 391(18), 1696–1708. https://doi.org/10.1056/NEJMoa2402604CrossRefPubMed

58.

Gross, N. D., Miller, D. M., Khushalani, N. I., Divi, V., Ruiz, E. S., Lipson, E. J., Meier, F., Su, Y. B., Swiecicki, P. L., Atlas, J., Geiger, J. L., Hauschild, A., Choe, J. H., Hughes, B. G. M., Schadendorf, D., Patel, V. A., Homsi, J., Taube, J. M., Lim, A. M., … Rischin, D. (2022). Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. New England Journal of Medicine, 387(17), 1557–1568. https://doi.org/10.1056/NEJMoa2209813CrossRefPubMed

59.

Nishizaki, D., Kurzrock, R., Miyashita, H., Adashek, J. J., Lee, S., Nikanjam, M., Eskander, R. N., Patel, H., Botta, G. P., Nesline, M. K., Pabla, S., Conroy, J. M., DePietro, P., Sicklick, J. K., & Kato, S. (2024). Viewing the immune checkpoint VISTA: Landscape and outcomes across cancers. ESMO Open, 9(4), 102942. https://doi.org/10.1016/j.esmoop.2024.102942CrossRefPubMedPubMedCentral

60.

Lim, J., Kurzrock, R., Nishizaki, D., Miyashita, H., Adashek, J. J., Lee, S., Pabla, S., Nesline, M., Conroy, J. M., DePietro, P., Lippman, S. M., amp; Kato, S. (2023). Pan-cancer analysis of TIM-3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity. Cancer Medicine, 13(1). https://doi.org/10.1002/cam4.6844

61.

Szeto, C. W., Kurzrock, R., Kato, S., Goloubev, A., Veerapaneni, S., Preble, A., Reddy, S. K., & Adashek, J. J. (2022). Association of differential expression of immunoregulatory molecules and presence of targetable mutations may inform rational design of clinical trials. ESMO Open, 7(1), 100396. https://doi.org/10.1016/j.esmoop.2022.100396CrossRefPubMedPubMedCentral

62.

Adashek, J. J., Kato, S., Nishizaki, D., Pabla, S., Nesline, M. K., Previs, R. A., Conroy, J. M., DePietro, P., & Kurzrock, R. (2024). LAG-3 transcriptomic expression correlates linearly with other checkpoints, but not with clinical outcomes. American Journal of Cancer Research, 14(1), 368–377.CrossRefPubMedPubMedCentral

63.

Adashek, J. J., Subbiah, V., Westphalen, C. B., Naing, A., Kato, S., & Kurzrock, R. (2023). Cancer: Slaying the nine-headed Hydra. Annals Of Oncology, 34(1), 61–69. https://doi.org/10.1016/j.annonc.2022.07.010CrossRefPubMed

64.

Adashek, J. J., Subbiah, V., & Kurzrock, R. (2021). From tissue-agnostic to N-of-one therapies: (R)Evolution of the precision paradigm. Trends Cancer, 7(1), 15–28. https://doi.org/10.1016/j.trecan.2020.08.009CrossRefPubMed

Title: Lessons learned from a decade of immune checkpoint inhibition: The good, the bad, and the ugly
Authors: Jacob J. Adashek
Jillian A. Moran
Dung T. Le
Razelle Kurzrock
Publication date: 01-06-2025
Publisher: Springer US
Keywords: Checkpoint Inhibitors
Adverse Effects of Cancer Therapy
Biomarkers
Published in: Cancer and Metastasis Reviews / Issue 2/2025
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-025-10260-8

CAR T-cells for acute leukemias in children: current status, challenges, and future directions

Leukemia
Review

Prostate cancer-specific proinflammatory cytokines and chemokines impact on cancer stem cell development, lineage plasticity and heterogeneity in an Ancestral/racially diverse population: review

Prostate Cancer
Review

VCAM-1 as a common biomarker in inflammatory bowel disease and colorectal cancer: unveiling the dual anti-inflammatory and anti-cancer capacities of anti-VCAM-1 therapies

Open Access
Inflammatory Bowel Disease
Review

Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy

Open Access
Osteosarcoma
Review

State-of-the-art of multidisciplinary approach of bone metastasis-directed therapy: review and challenging questions for preparation of a GEMO practice guidelines

Open Access
Radiotherapy
Review

Tumor heterogeneity in retinoblastoma: a literature review

Open Access
Retinoblastoma
Review

Women’s health knowledge hub

Menopause
Clinical Collection

Elevate your patient care with our comprehensive, evidence-based medical education on women's health. Designed to help you provide exceptional care for your female patients at every stage of life, we provide expert insights into topics such as reproductive health, menopause, breast cancer and sex-specific health risks and precision medicine.

Genetic Testing
On-demand Webinar

In this interactive webinar, experts Dr. Subbiah, Dr. Drilon, and Dr. Williams discuss best pathological practices within NSCLC and thyroid cancer, as well as how genomic testing can improve outcomes in clinical practice, using patient case studies as illustrations.

This content is intended only for US-based healthcare providers.

Supported by:

Illumina, Inc., and Eli Lilly and Company

Dr. Vivek Subbiah

Dr. Alexander Drilon

Dr. Michelle Williams

Developed by: Springer Healthcare

Watch now

Elevate your expertise in aplastic anemia (Link opens in a new window)

Aplastic Anemia
Independent Medical Education

Transform the way you care for your patients with aplastic anemia with our 3-module series using real-world case studies and expert insights. Discover why early diagnosis matters, explore the benefits and risks of current treatments, and develop tailored approaches for complex cases.

Supported by:

Pfizer

Developed by: Springer Healthcare IME

Learn more

Navigating neuroimaging in Alzheimer disease care

Springer Medicine

Lessons learned from a decade of immune checkpoint inhibition: The good, the bad, and the ugly

Abstract

Other articles of this Issue 2/2025

CAR T-cells for acute leukemias in children: current status, challenges, and future directions

Prostate cancer-specific proinflammatory cytokines and chemokines impact on cancer stem cell development, lineage plasticity and heterogeneity in an Ancestral/racially diverse population: review

VCAM-1 as a common biomarker in inflammatory bowel disease and colorectal cancer: unveiling the dual anti-inflammatory and anti-cancer capacities of anti-VCAM-1 therapies

Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy

State-of-the-art of multidisciplinary approach of bone metastasis-directed therapy: review and challenging questions for preparation of a GEMO practice guidelines

Tumor heterogeneity in retinoblastoma: a literature review

Women’s health knowledge hub

Incorporating comprehensive genomic profiling into the standard-of-care for NSCLC and thyroid cancer

Elevate your expertise in aplastic anemia (Link opens in a new window)

Navigating neuroimaging in Alzheimer disease care

Springer Medicine

Abstract

Please log in to get access to this content