Dysfunction of HPV16-specific CD8+ T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29909905
DOI
10.1016/j.oraloncology.2018.05.010
PII: S1368-8375(18)30194-5
Knihovny.cz E-resources
- Keywords
- Human papillomavirus, Oropharyngeal cancer, PD-1, Tim-3, Tumor-infiltrating lymphocytes,
- MeSH
- Programmed Cell Death 1 Receptor antagonists & inhibitors metabolism MeSH
- Hepatitis A Virus Cellular Receptor 2 metabolism MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- Cytokines biosynthesis MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Human papillomavirus 16 isolation & purification MeSH
- Oropharyngeal Neoplasms drug therapy immunology metabolism virology MeSH
- Nivolumab therapeutic use MeSH
- Antineoplastic Agents, Immunological therapeutic use MeSH
- Aged MeSH
- Lymphocytes, Tumor-Infiltrating immunology MeSH
- Tumor Escape MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Programmed Cell Death 1 Receptor MeSH
- Hepatitis A Virus Cellular Receptor 2 MeSH
- Cytokines MeSH
- HAVCR2 protein, human MeSH Browser
- Nivolumab MeSH
- PDCD1 protein, human MeSH Browser
- Antineoplastic Agents, Immunological MeSH
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 IFNγ upon specific stimulation and predominantly expressed PD-1 but not Tim-3. Specific IFNγ 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.
CRCINA INSERM U1232 Université de Nantes 8 Quai Moncousu 44007 Nantes France
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