Biomarkers for immunotherapy resistance in non-small cell lung cancer
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 inhibi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1489977/full |
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| author | Catriona Rother Tom John Annie Wong Annie Wong |
| author_facet | Catriona Rother Tom John Annie Wong Annie Wong |
| author_sort | Catriona Rother |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2cb50fa06a7b47708ec95bcd7e9fdfdf |
| institution | OA Journals |
| issn | 2234-943X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-2cb50fa06a7b47708ec95bcd7e9fdfdf2025-08-20T01:58:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-12-011410.3389/fonc.2024.14899771489977Biomarkers for immunotherapy resistance in non-small cell lung cancerCatriona Rother0Tom John1Annie Wong2Annie Wong3Wellington Blood and Cancer Centre, Te Whatu Ora Capital, Wellington, New ZealandDepartment of Medical Oncology, Peter MacCallum, Cancer Centre, Melbourne, VIC, AustraliaWellington Blood and Cancer Centre, Te Whatu Ora Capital, Wellington, New ZealandDepartment of Medicine, University of Otago, Wellington, New ZealandImmunotherapy 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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1489977/fullnon-small cell lung cancer (NSCLC)immunotherapy resistanceprecision oncology strategiesbiomarkerscirculating biomarkers |
| spellingShingle | Catriona Rother Tom John Annie Wong Annie Wong Biomarkers for immunotherapy resistance in non-small cell lung cancer Frontiers in Oncology non-small cell lung cancer (NSCLC) immunotherapy resistance precision oncology strategies biomarkers circulating biomarkers |
| title | Biomarkers for immunotherapy resistance in non-small cell lung cancer |
| title_full | Biomarkers for immunotherapy resistance in non-small cell lung cancer |
| title_fullStr | Biomarkers for immunotherapy resistance in non-small cell lung cancer |
| title_full_unstemmed | Biomarkers for immunotherapy resistance in non-small cell lung cancer |
| title_short | Biomarkers for immunotherapy resistance in non-small cell lung cancer |
| title_sort | biomarkers for immunotherapy resistance in non small cell lung cancer |
| topic | non-small cell lung cancer (NSCLC) immunotherapy resistance precision oncology strategies biomarkers circulating biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1489977/full |
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