期刊
ONCOIMMUNOLOGY
卷 4, 期 1, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/21624011.2014.965570
关键词
CD8(+) T lymphocytes; HNSCC; HPV; PD-1; Tim-3
资金
- Grant Agency of the Ministry of Health of the Czech Republic [NT 11542]
- GAUK from Charles University [5734/2012]
- University Hospital Motol, Prague, Czech Republic [00064203]
- Biocev
- Academy of Science
- Charles University [CZ.1.05/1.1.00/02.0109]
- European Regional Development Fund
- [SVV 266513]
- [UNCE 204013]
- [PRVOUK 27-1]
Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naive, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFN gamma(+) CD8(+) T lymphocytes, IL-17(+) CD8(+) T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of Cox-2 mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.
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