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Review
. 2025 Apr 4;44(2):43.
doi: 10.1007/s10555-025-10260-8.

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

Jacob J Adashek  1 , Jillian A Moran  2 , Dung T Le  3 , Razelle Kurzrock  4   5   6
Affiliations
Review

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

Jacob J Adashek et al. Cancer Metastasis Rev. .

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.

Keywords: Hyperprogressive disease; Immune checkpoint inhibition; Immune-related adverse events.

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Conflict of interest statement

Declarations. Competing interests: Jacob J. Adashek serves on the advisory board of CureMatch Inc and as a consultant for datma. Jillian A. Moran has no disclosures to report. Dung T. Le serves as a consultant for Merck, Bristol Myers Squibb, Nouscom, G1 Therapeutics, Janssen, Regeneron, Tavotek Biotherapeutics, Catenion, Bayer, Sirtex, Tango Therapeutics, Endeavor Biosciences, and Merus and has received research funding from Merck, Bristol Myers Squibb, Curegenix, Nouscom, Medivir, and Abbvie. She has received speaking honoraria from Merck and is an inventor of licensed intellectual property related to technology for mismatch repair deficiency for diagnosis and therapy (WO2016077553 A1) from Johns Hopkins University. The terms of these arrangements are being managed by Johns Hopkins. Razelle Kurzrock has received research funding from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, and TopAlliance and from the NCI; as well as consultant and/or speaker fees and/or advisory board/consultant for Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Inc., Biological Dynamics, Caris, Datar Cancer Genetics, Daiichi, EISAI, EOM Pharmaceuticals, Iylon, LabCorp, Merck, NeoGenomics, Neomed, Pfizer, Precirix, Prosperdtx, Regeneron, Roche, TD2/Volastra, Turning Point Therapeutics, X-Biotech; has an equity interest in CureMatch Inc.; serves on the Board of CureMatch and CureMetrix, and is a co-founder of CureMatch.

Figures

Fig. 1
Fig. 1
Immune checkpoint inhibitors have a complicated array of effects
See this image and copyright information in PMC

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