Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 20:12:817548.
doi: 10.3389/fonc.2022.817548. eCollection 2022.

The Landscape of Immunotherapy Resistance in NSCLC

Daniele Frisone  1 , Alex Friedlaender  1   2 , Alfredo Addeo  1   3 , Petros Tsantoulis  1   3
Affiliations
Review

The Landscape of Immunotherapy Resistance in NSCLC

Daniele Frisone et al. Front Oncol. .

Erratum in

Abstract

Lung cancer is the leading cause of cancer mortality worldwide. Immunotherapy has demonstrated clinically significant benefit for non-small-cell lung cancer, but innate (primary) or acquired resistance remains a challenge. Criteria for a uniform clinical definition of acquired resistance have been recently proposed in order to harmonize the design of future clinical trials. Several mechanisms of resistance are now well-described, including the lack of tumor antigens, defective antigen presentation, modulation of critical cellular pathways, epigenetic changes, and changes in the tumor microenvironment. Host-related factors, such as the microbiome and the state of immunity, have also been examined. New compounds and treatment strategies are being developed to target these mechanisms with the goal of maximizing the benefit derived from immunotherapy. Here we review the definitions of resistance to immunotherapy, examine its underlying mechanisms and potential corresponding treatment strategies. We focus on recently published clinical trials and trials that are expected to deliver results soon. Finally, we gather insights from recent preclinical discoveries that may translate to clinical application in the future.

Keywords: NSCLC; checkpoint inhibitor; immunotherapy; lung cancer; resistance.

PubMed Disclaimer

Conflict of interest statement

AF: Advisory board with Roche, Pfizer, Astellas, AstraZeneca, MSD, Sanofi, Novartis and BMS. AA: Advisory board: MSD Oncology, Roche, Takeada, Pfizer, Bristol-Myers Squibb, AstraZeneca, Eli-Lilly, Roche. Speaker Bureau: Eli-Lilly, AstraZeneca.PT: Advisory board with Astellas, Bayer, BMS, Ipsen, Janssen-Cilag, Merck, MSD, Pfizer, Roche and Sanofi. Travel and conference expenses from Lilly, Janssen-Cilag and Sanofi. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of resistance to immunotherapy and main molecular pathways involved.
See this image and copyright information in PMC

References

    1. GLOBOCAN 2018. Available at: https://gco.iarc.fr/.
    1. Früh M, De Ruysscher D, Popat S, Crinò L, Felip E, Peters S, et al. . Small-Cell Lung Cancer (SCLC): ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann Oncol (2013) 24 Suppl 6:vi99–105. doi: 10.1093/annonc/mdt178 - DOI - PubMed
    1. Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB, Ahn MJ, et al. . Five-Year Overall Survival for Patients With Advanced Nonsmall-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol (2019) 37:2518–27. doi: 10.1200/JCO.19.00934 - DOI - PMC - PubMed
    1. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. . Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non-Small Cell Lung Cancer Treated With Nivolumab. JAMA Oncol (2019) 5:1411–20. doi: 10.1001/jamaoncol.2019.2187 - DOI - PMC - PubMed
    1. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. . Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol (2019) 37:537–46. doi: 10.1200/JCO.18.00149 - DOI - PubMed

LinkOut - more resources