A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP)Publisher
BMJ Publishing Group LtdDate
2020-09-07Citation
10.1136/jitc-2020-001187
Journal for Immunotherapy of Cancer 8.2 (2020): e00118
ISSN
2051-1426DOI
10.1136/jitc-2020-001187Funded by
This work was supported by grants to AA: FIS PI15/01491 and CIBER CARDIOVASCULAR from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III with co-funding from the Fondo Europeo de Desarrollo Regional; FEDER)Project
Gobierno de España. PI15/01491Editor's Version
http://dx.doi.org/10.1136/jitc-2020-001187Subjects
adaptive immunity; humoral; immunity; immunotherapy; lung neoplasms; tumor escape; MedicinaRights
© 2020 Author(s) (or their employer(s))Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Background Lung 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. Methods We 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. Results We 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. Conclusion These findings unveil a novel mechanism of action for anti-PD-1 therapy and provide new targets for optimization of current therapies against lung cancer.
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Google Scholar:Sánchez-Alonso, Santiago
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Setti-Jerez, Giulia
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Arroyo, Montserrat
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Hernández, Tathiana
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Martos, Ma Inmaculada
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Sánchez-Torres, Jose Miguel
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Colomer Bosch, Ramón
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Ramiro, Almudena R.
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Alfranca González, Arantzazu
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