Expanding indications of immune checkpoint inhibitors: a decade of success going strong
TL;DR
Limited benefit in other cancer subsets highlights the need for biomarker discovery and optimization of therapeutic strategies, including addition of antibody-drug conjugates to ICIs, next-generation checkpoint modulation, personalized neoantigen vaccines, and engineered cellular immunotherapy.
Abstract
ABSTRACT Introduction Immune checkpoint inhibitors (ICIs) have transformed oncology by targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1), thereby enabling responses across multiple malignancies. Despite these advances, benefits remain limited in many cancers. Areas covered A narrative literature review was conducted using PubMed, Embase, and the Cochrane Library to identify English-language publications from 1 January 2000, through 31 December 2025. Eligible sources included pivotal trials, real-world studies, reviews, and relevant clinical practice guidelines. Expert opinion Since 2011, ICIs have permeated virtually all fields of oncology, with meaningful impact across many cancer types. Beyond expanding indications, they offer potential for durable benefit in many responders. In melanoma, head and neck, kidney, liver, and urothelial cancers, PD-L1 testing outside clinical trials is no longer required. Tumor-agnostic efficacy of PD-1 ± CTLA-4 inhibition in microsatellite instability-high cancers is well established. Limited benefit in other cancer subsets highlights the need for biomarker discovery and optimization of therapeutic strategies, including addition of antibody-drug conjugates to ICIs, next-generation checkpoint modulation, personalized neoantigen vaccines, and engineered cellular immunotherapy. Effective future therapies should also address comprehensive profiling of tumor cells, their molecular expression patterns, and constantly changing dynamics of the tumor microenvironment.