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oai:docta.ucm.es:20.500.14352/733722024-10-09T16:38:22Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Ramos Paradas, Javier author Gómez Sánchez, David author Rosado, Aranzazu author Ucero Herrería, Álvaro Conrado author Ferrer, Irene author García Luján, Ricardo author Zugazagoitia Fraile, Jon author Carrizo, Nuria author Enguita Valls, Ana Belén author Conde Gallego, Esther author Garrido Martín, Eva María author Paz-Ares Rodríguez, Luis Gonzaga author 2022-03-09 Lung cancer is the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent histology. While immunotherapy with checkpoint inhibitors has shown outstanding results in NSCLC, the precise identification of responders remains a major challenge. Most studies attempting to overcome this handicap have focused on adenocarcinomas or squamous cell carcinomas. Among NSCLC subtypes, the molecular and immune characteristics of lung large cell carcinoma (LCC), which represents 10% of NSCLC cases, are not well defined. We hypothesized that specific molecular aberrations may impact the immune microenvironment in LCC and, consequently, the response to immunotherapy. To that end, it is particularly relevant to thoroughly describe the molecular genotype–immunophenotype association in LCC–to identify robust predictive biomarkers and improve potential benefits from immunotherapy. We established a cohort of 18 early-stage, clinically annotated, LCC cases. Their molecular and immune features were comprehensively characterized by genomic and immune-targeted sequencing panels along with immunohistochemistry of immune cell populations. Unbiased clustering defined two novel subgroups of LCC. Pro-immunogenic tumors accumulated certain molecular alterations, showed higher immune infiltration and upregulated genes involved in potentiating immune responses when compared to pro-tumorigenic samples, which favored tumoral progression. This classification identified a set of biomarkers that could potentially predict response to immunotherapy. These results could improve patient selection and expand potential benefits from immunotherapy. Ramos Paradas, J., Gómez Sánchez, D., Rosado, A. et al. «Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy». Journal of Clinical Medicine, vol. 11, n.o 6, marzo de 2022, p. 1500. Crossref, https://doi.org/10.3390/jcm11061500. 2077-0383 10.3390/jcm11061500 https://hdl.handle.net/20.500.14352/73372 https://doi.org/10.3390/jcm11061500 https://www.mdpi.com/2077-0383/11/6/1500 Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy