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Publications

Journal Article Review Epublish 2 citations

PubMed: 39749035 DOI: 10.3389/fonc.2024.1489977

Biomarkers for immunotherapy resistance in non-small cell lung cancer.

Front Oncol 14:1489977

Authors: Catriona Rother, Tom John, Annie Wong

Affiliations

  • Wellington Blood and Cancer Centre, Te Whatu Ora Capital, Wellington, New Zealand.
  • Department of Medical Oncology, Peter MacCallum, Cancer Centre, Melbourne, VIC, Australia.
  • Department of Medicine, University of Otago, Wellington, New Zealand.

Abstract

Immunotherapy has revolutionised the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving survival outcomes and offering renewed hope to patients with advanced disease. However, the majority of patients experience limited long-term benefits from immune checkpoint inhibition (ICI) due to the development of primary or acquired immunotherapy resistance. Accurate predictive biomarkers for immunotherapy resistance are essential for individualising treatment strategies, improving survival outcomes, and minimising potential treatment-related harm. This review discusses the mechanisms underlying resistance to immunotherapy, addressing both cancer cell-intrinsic and cancer cell-extrinsic resistance processes. We summarise the current utility and limitations of two clinically established biomarkers: programmed death ligand 1 (PD-L1) expression and tumour mutational burden (TMB). Following this, we present a comprehensive review of emerging immunotherapy biomarkers in NSCLC, including tumour neoantigens, epigenetic signatures, markers of the tumour microenvironment (TME), genomic alterations, host-microbiome composition, and circulating biomarkers. The potential clinical applications of these biomarkers, along with novel approaches to their biomarker identification and targeting, are discussed. Additionally, we explore current strategies to overcome immunotherapy resistance and propose incorporating predictive biomarkers into an adaptive clinical trial design, where specific immune signatures guide subsequent treatment selection.

MeSH

Cells, Lung, Neoplasms, Carcinoma, Non-Small-Cell Lung, Biomarkers, Immunotherapy, Lung Neoplasms, Small Cell Lung Carcinoma, Therapeutics

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