Immunomodulatory role of oncogenic alterations in non-small cell lung cancer: a review of implications for immunotherapy


Por: Ramos-Ramírez M., Caballe-Pérez E., Lucio-Lozada J., Romero-Nuñez E., Castillo-Ruiz C., Dorantes-Sánchez L., Flores-Estrada D., Recondo G., Barrios-Bernal P., Cabrera-Miranda L., Bravo-Dominguez H., Hernández-Pedro N., Arrieta O.

Publicada: 1 ene 2025
Resumen:
Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in patients with non-small cell lung cancer (NSCLC) lacking targetable oncogenic alterations. However, their efficacy in individuals with such genomic alterations remains heterogeneous and poorly understood. In detail, certain oncogenic alterations in TP53, EGFR (uncommon mutations), KRAS (G12C), BRAF (non-V600E), MET (amplifications), FGFR1 and FGFR4, actively modify MAPK, PI3K, and STING signaling, thus remodeling tumoral immune phenotype and are associated with high TMB counts, enriched T lymphocyte tumor infiltration, and high expression of antigen-presenting molecules, supporting their consideration as part of the eligibility criteria for ICIs treatment. Nonetheless, other oncogenic alterations are associated with an immunosuppressive TME, low TMB counts, and downregulation of targetable immune checkpoints, in which novel therapeutic approaches are currently being tested to overcome their intrinsic resistance. In this context, this review discusses the fundamental mechanisms by which frequent driver alterations affect ICIs efficacy in patients with NSCLC, and outlines their prognostic relevance in the era of immunotherapy. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

Filiaciones:
Ramos-Ramírez M.:
 Thoracic Oncology Functional Unit (UFOT), Instituto Nacional de Cancerología, (INCAN), (CDMX), Mexico City, Mexico

Caballe-Pérez E.:
 Thoracic Oncology Functional Unit (UFOT), Instituto Nacional de Cancerología, (INCAN), (CDMX), Mexico City, Mexico

Lucio-Lozada J.:
 Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), (CDMX), Mexico City, Mexico

Romero-Nuñez E.:
 Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), (CDMX), Mexico City, Mexico

Castillo-Ruiz C.:
 Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), (CDMX), Mexico City, Mexico

Dorantes-Sánchez L.:
 Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), (CDMX), Mexico City, Mexico

Flores-Estrada D.:
 Thoracic Oncology Functional Unit (UFOT), Instituto Nacional de Cancerología, (INCAN), (CDMX), Mexico City, Mexico

Recondo G.:
 Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, United States

Barrios-Bernal P.:
 Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), (CDMX), Mexico City, Mexico

Cabrera-Miranda L.:
 Thoracic Oncology Functional Unit (UFOT), Instituto Nacional de Cancerología, (INCAN), (CDMX), Mexico City, Mexico

Bravo-Dominguez H.:
 Thoracic Oncology Functional Unit (UFOT), Instituto Nacional de Cancerología, (INCAN), (CDMX), Mexico City, Mexico

Hernández-Pedro N.:
 Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), (CDMX), Mexico City, Mexico

 Thoracic Oncology Functional Unit (UFOT), Instituto Nacional de Cancerología, (INCAN), (CDMX), Mexico City, Mexico

Arrieta O.:
 Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), (CDMX), Mexico City, Mexico

 Thoracic Oncology Functional Unit (UFOT), Instituto Nacional de Cancerología, (INCAN), (CDMX), Mexico City, Mexico
ISSN: 01677659
Editorial
SPRINGER, VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS, Países Bajos
Tipo de documento: Review
Volumen: 44 Número: 1
Páginas:
WOS Id: 001414994100001
ID de PubMed: 39915358

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