RT Journal Article
T1 Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy
A1 Ramos Paradas, Javier
A1 Gómez Sánchez, David
A1 Rosado, Aranzazu
A1 Ucero Herrería, Álvaro Conrado
A1 Ferrer, Irene
A1 García Luján, Ricardo
A1 Zugazagoitia Fraile, Jon
A1 Carrizo, Nuria
A1 Enguita Valls, Ana Belén
A1 Conde Gallego, Esther
A1 Garrido Martín, Eva María
A1 Paz-Ares Rodríguez, Luis Gonzaga
AB 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.
PB MDPI
SN 2077-0383
YR 2022
FD 2022-03-09
LK https://hdl.handle.net/20.500.14352/73372
UL https://hdl.handle.net/20.500.14352/73372
LA eng
NO 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.
NO Unión Europea
NO Ministerio de Educación, Formación Profesional y Deportes (España)
NO Comunidad de Madrid
NO Bristol Myers Squibb
NO Centro de Investigación Biomédica en Red de Cáncer
NO Asociación Española Contra el Cáncer
NO European Respiratory Society
NO Fundación CRIS contra el cáncer (Unidad Integral CRIS de Inmuno-oncología)
DS Docta Complutense
RD 10 abr 2025