Faculty, Staff and Student Publications

Publication Date

6-1-2024

Journal

Trends in Pharmacological Sciences

DOI

10.1016/j.tips.2024.04.006

PMID

38744552

PMCID

PMC11189143

PubMedCentral® Posted Date

6-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Immune checkpoint blockade (ICB) therapy works by inhibiting suppressive checkpoints that become upregulated after T cell activation, like PD-1/PD-L1 and CTLA-4. While the initial FDA approvals of ICB have revolutionized cancer therapies and fueled a burgeoning immuno-oncology field, more recent clinical development of new agents has been slow. Here, focusing on lung cancer, we review the latest research uncovering tumor cell intrinsic and extrinsic ICB resistance mechanisms as major hurdles to treatment efficacy and clinical progress. These include genomic and non-genomic tumor cell alterations, along with host and microenvironmental factors like the microbiome, metabolite accumulation, and hypoxia. Together, these factors can cooperate to promote immunosuppression and ICB resistance. Opportunities to prevent resistance are constantly evolving in this rapidly expanding field, with the goal of moving toward personalized immunotherapeutic regimens.

Keywords

Humans, Immune Checkpoint Inhibitors, Lung Neoplasms, Drug Resistance, Neoplasm, Animals, Tumor Microenvironment, Immunotherapy, Immune checkpoint blockade, Lung cancer, Resistance mechanisms, Combination therapy strategies

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.