Dysfunction of HPV16-specific CD8+ T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
29909905
DOI
10.1016/j.oraloncology.2018.05.010
PII: S1368-8375(18)30194-5
Knihovny.cz E-zdroje
- Klíčová slova
- Human papillomavirus, Oropharyngeal cancer, PD-1, Tim-3, Tumor-infiltrating lymphocytes,
- MeSH
- antigeny CD279 antagonisté a inhibitory metabolismus MeSH
- buněčný receptor 2 viru hepatitidy A metabolismus MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- cytokiny biosyntéza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský papilomavirus 16 izolace a purifikace MeSH
- nádory orofaryngu farmakoterapie imunologie metabolismus virologie MeSH
- nivolumab terapeutické užití MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- senioři MeSH
- tumor infiltrující lymfocyty imunologie MeSH
- únik nádoru z imunitní kontroly MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD279 MeSH
- buněčný receptor 2 viru hepatitidy A MeSH
- cytokiny MeSH
- HAVCR2 protein, human MeSH Prohlížeč
- nivolumab MeSH
- PDCD1 protein, human MeSH Prohlížeč
- protinádorové látky imunologicky aktivní 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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