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Dysfunction of HPV16-specific CD8+T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1
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SYSNO ASEP 0497022 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Dysfunction of HPV16-specific CD8+T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1 Tvůrce(i) Hladíková, K. (CZ)
Partlová, S. (CZ)
Koucký, V. (CZ)
Bouček, Jan (MBU-M)
Fonteneau, J.F. (FR)
Zábrodský, M. (CZ)
Tachezy, R. (CZ)
Grega, M. (CZ)
Špíšek, R. (CZ)
Fialová, A. (CZ)Zdroj.dok. Oral Oncology. - : Elsevier - ISSN 1368-8375
Roč. 82, JUL (2018), s. 75-82Poč.str. 8 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova Oropharyngeal cancer ; Human papillomavirus ; PD-1 Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology CEP NV16-28600A GA MZd - Ministerstvo zdravotnictví LQ1604 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora MBU-M - RVO:61388971 UT WOS 000436776400012 EID SCOPUS 85047095675 DOI 10.1016/j.oraloncology.2018.05.010 Anotace 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.
Methods: 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.
Results: 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.
Conclusion: 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.Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2019
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