Dysfunction of HPV16-specific CD8+T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F18%3A00497022" target="_blank" >RIV/61388971:_____/18:00497022 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/18:10375431 RIV/00216208:11130/18:10375431 RIV/00216208:11310/18:10375431 RIV/00064203:_____/18:10375431

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.oraloncology.2018.05.010" target="_blank" >http://dx.doi.org/10.1016/j.oraloncology.2018.05.010</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.oraloncology.2018.05.010" target="_blank" >10.1016/j.oraloncology.2018.05.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dysfunction of HPV16-specific CD8+T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1

Popis výsledku v původním jazyce

Background: Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients. nMethods: Tumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3. nResults: HPV16-specific tumor-infiltrating T cells were present in 73.1% of HPV-associated oropharyngeal tumors. HPV16 specific CD8 + TILs were able to produce IFN gamma upon specific stimulation and predominantly expressed PD-1 but not Tim-3. Specific IFN gamma production was further enhanced after a blockade of both PD-1 and Tim-3 pathways but not after a PD-1 blockade alone. Additionally, the specific stimulation of anti-HPV16 CD8 + T cells suppressed Tim-3 upregulation after the PD-1 blockade. nConclusion: Our data provide the rationale for combination cancer immunotherapy approaches, including the dual blockade of PD-1 and Tim-3 and, potentially, the use of HPV16-directed therapeutic vaccines.

Název v anglickém jazyce

Dysfunction of HPV16-specific CD8+T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1

Popis výsledku anglicky

Background: Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients. nMethods: Tumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3. nResults: HPV16-specific tumor-infiltrating T cells were present in 73.1% of HPV-associated oropharyngeal tumors. HPV16 specific CD8 + TILs were able to produce IFN gamma upon specific stimulation and predominantly expressed PD-1 but not Tim-3. Specific IFN gamma production was further enhanced after a blockade of both PD-1 and Tim-3 pathways but not after a PD-1 blockade alone. Additionally, the specific stimulation of anti-HPV16 CD8 + T cells suppressed Tim-3 upregulation after the PD-1 blockade. nConclusion: Our data provide the rationale for combination cancer immunotherapy approaches, including the dual blockade of PD-1 and Tim-3 and, potentially, the use of HPV16-directed therapeutic vaccines.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

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)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Oral Oncology

ISSN

1368-8375

e-ISSN

—

Svazek periodika

82

Číslo periodika v rámci svazku

JUL

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

75-82

Kód UT WoS článku

000436776400012

EID výsledku v databázi Scopus

2-s2.0-85047095675