Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy

Journal of Clinical Medicine

卷:11

Eva M. Garrido-Martin¹  Alvaro C. Ucero¹  Aranzazu Rosado¹  David Gómez-Sánchez¹  Nuria Carrizo¹  Javier Ramos-Paradas¹  Luis Paz-Ares¹  Irene Ferrer¹  Jon Zugazagoitia²  Ana B. Enguita³  Ricardo García-Luján⁴  Esther Conde⁵ 

[1] H12O-CNIO Lung Cancer Clinical Research Unit, Health Research Institute Hospital 12 de Octubre (imas12)/Spanish National Cancer Research Center (CNIO), 28041 Madrid, Spain;

[2] Medical Oncology Department, 12 de Octubre Hospital, 28041 Madrid, Spain;

[3] Pathology Department, 12 de Octubre Hospital, 28041 Madrid, Spain;

[4] Pulmonary Department, 12 de Octubre Hospital, 28041 Madrid, Spain;

[5] Spanish Center for Biomedical Research Network in Oncology (CIBERONC), 28029 Madrid, Spain;

关键词: non-small cell lung cancer;    lung large cell carcinoma;    immunotherapy;    checkpoint inhibitors;    multiparametric analysis;    predictive biomarkers;   

DOI  :  10.3390/jcm11061500

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown