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

0497022 - MBÚ 2019 RIV NL eng J - Článek v odborném periodiku
Hladíková, K. - Partlová, S. - Koucký, V. - Bouček, Jan - Fonteneau, J.F. - Zábrodský, M. - Tachezy, R. - Grega, M. - Špíšek, R. - Fialová, A.
Dysfunction of HPV16-specific CD8+T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1.
Oral Oncology. Roč. 82, JUL (2018), s. 75-82. ISSN 1368-8375. E-ISSN 1879-0593
Grant CEP: GA MZd(CZ) NV16-28600A; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:61388971
Klíčová slova: Oropharyngeal cancer * Human papillomavirus * PD-1
Obor OECD: Microbiology
Impakt faktor: 3.730, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0289637