Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8(+) T cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10399095" target="_blank" >RIV/00064203:_____/19:10399095 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10399095 RIV/00216208:11130/19:10399095 RIV/00216208:11150/19:10399095 RIV/00179906:_____/19:10399095

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ywfn4~Chm7" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ywfn4~Chm7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s40425-019-0726-6" target="_blank" >10.1186/s40425-019-0726-6</a>

Result language

angličtina

Original language name

Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8(+) T cells

Original language description

Background Standard treatment of oropharyngeal squamous cell carcinoma (OPSCC) is associated with high morbidity, whereas immunotherapeutic approaches using PD-1:PD-L1 checkpoint blockade only show moderate response rates in OPSCC patients. Therefore, a better stratification of patients and the development of novel therapeutic protocols are crucially needed. The importance of tumor-infiltrating B cells (TIL-Bs) in shaping antitumor immunity remains unclear; therefore, we analyzed frequency, phenotype, prognostic value and possible roles of TIL-Bs in OPSCC. Methods We utilized transcriptomic analysis of immune response-related genes in 18 OPSCC samples with respect to human papillomavirus (HPV) status. The density and localization of CD20(+), CD8(+) and DC-LAMP(+) cells were subsequently analyzed in 72 tissue sections of primary OPSCC samples in relation to patients&apos; prognosis. The immunohistochemical approach was supplemented by flow cytometry-based analysis of phenotype and functionality of TIL-Bs in freshly resected primary OPSCC tissues. Results We observed significantly higher expression of B cell-related genes and higher densities of CD20(+) B cells in HPV-associated OPSCC samples. Interestingly, CD20(+) TIL-Bs and CD8(+) T cells formed non-organized aggregates with interacting cells within the tumor tissue. The densities of both intraepithelial CD20(+) B cells and B cell/CD8(+) T cell interactions showed prognostic significance, which surpassed HPV positivity and CD8(+) TIL density in stratification of OPSCC patients. High density of TIL-Bs was associated with an activated B cell phenotype, high CXCL9 production and high levels of tumor-infiltrating CD8(+) T cells. Importantly, the abundance of direct B cell/CD8(+) T cell interactions positively correlated with the frequency of HPV16-specific CD8(+) T cells, whereas the absence of B cells in tumor-derived cell cultures markedly reduced CD8(+) T cell survival. Conclusions Our results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8(+) T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8(+) T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8(+) T cells in the tumor microenvironment.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal for ImmunoTherapy of Cancer

ISSN

2051-1426

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

261

UT code for WoS article

000491002000001

EID of the result in the Scopus database

2-s2.0-85073513894