Abstract
BackgroundLung cancer is one of the most frequent malignancies in humans and is a major cause of death. A number of therapies aimed at reinforcing antitumor immune response, including antiprogrammed cell death protein 1 (anti-PD-1) antibodies, are successfully used to treat several neoplasias as non-small cell lung cancer (NSCLC). However, host immune mechanisms that participate in response to anti-PD-1 therapy are not completely understood.MethodsWe used a syngeneic immunocompetent mouse model of NSCLC to analyze host immune response to anti-PD-1 treatment in secondary lymphoid organs, peripheral blood and tumors, by flow cytometry, immunohistochemistry and quantitative real-time PCR (qRT-PCR). In addition, we also studied specific characteristics of selected immune subpopulations in ex vivo functional assays.ResultsWe show that anti-PD-1 therapy induces a population of circulating T follicular helper cells (cTfh) with enhanced B activation capacity, which participates in tumor response to treatment. Anti-PD-1 increases the number of tertiary lymphoid structures (TLS), which correlates with impaired tumor growth. Of note, TLS support cTfh-associated local antibody production, which participates in host immune response against tumor.ConclusionThese findings unveil a novel mechanism of action for anti-PD-1 therapy and provide new targets for optimization of current therapies against lung cancer.
Funder
Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional, FEDER
Subject
Cancer Research,Pharmacology,Oncology,Molecular Medicine,Immunology,Immunology and Allergy
Cited by
32 articles.
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