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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Journal for ImmunoTherapy of Cancer

ISSN

2051-1426

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

261

Kód UT WoS článku

000491002000001

EID výsledku v databázi Scopus

2-s2.0-85073513894