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
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