V posledních několika letech se významně změnil pohled na biologickou podstatu nádorů v oblasti hlavy a krku. Klasickými prokázanými rizikovými faktory nádorů v oblasti hlavy a krku jsou kouření a konzumace alkoholu, resp. jejich kombinace. Pacienti s nádory vzniklými na podkladě této etiologie se pohybují ve vyšších věkových skupinách, nejčastěji v pátém a šestém decéniu. Dále byla v posledních přibližně 15 letech prokázána souvislost s infekcí lidským papillomavirem (HPV), který je dnes považován za jeden z nejvýznamnějších rizikových faktorů, zejména pro karcinom orofaryngu. HPV pozitivní nádory orofaryngu jsou spojeny s významně lepší prognózou onemocnění. Výzkumná i klinická data ukazují, že HPV pozitivní a negativní nádory lze v mnoha ohledech považovat za dvě rozdílné entity a dosud není zcela objasněno, jaké faktory jsou klíčové pro lepší prognózu HPV pozitivní nádorů. Jedním z důležitých faktorů, který se podílí na rozdílné prognóze, může být charakter imunitní reakce. Tento článek shrnuje současné poznatky o různých aspektech protinádorové imunitní reakce u HPV pozitivních a negativních nádorů. Současné studie udávají, že téměř u všech HPV pozitivních pacientů byly detekovány významné počty HPV specifických T lymfocytů, v nádorové tkáni. I navzdory tomu však dochází k rozvoji nádoru, což může být způsobeno abnormalitami v antigenní prezentaci, dysfunkcemi T lymfocytů či přítomností různých populací imunosupresivních buněk. Imunologický profil HPV pozitivních, resp. HPV negativních nádorů v oblasti hlavy a krku přesto jednoznačně koreluje s terapeutickými výsledky a HPV specifická imunitní odpověď má pravděpodobně zásadní význam při lepší odpovědi HPV pozitivních pacientů na konvenční léčbu. Diskutujeme také vyvíjené postupy HPV specifické protinádorové imunoterapie, které jsou nyní ve fázi klinických zkoušek.
The insight into the biological nature of head and neck squamous cell carcinoma has evolved significantly in the last few years. Tobacco use and alcohol consumption are proven risk factors of head and neck squamous cell carcinoma. Cancer patients possessing such a tumor are generally elderly, mostly in fifth or sixth decade of life. In addition, significant association of head and neck squamous cell carcinoma with infection by human papillomavirus (HPV) was proven. HPV is now considered to be one of the most important risk factors, particularly for oropharyngeal carcinoma. HPV‑positive tumors of oropharynx are associated with significantly better prognosis. Experimental and clinical data indicate that HPV‑positive and HPV‑negative tumors can be considered as two different entities and it has not been clarified which factors are crucial for better prognosis of HPV‑positive tumors. The character of immune reaction, which contributes to distinct prognosis, may be one of the important factors. This review summarizes current knowledge concerning various aspects of anti‑tumor immune responses in HPV‑positive and HPV‑negative tumors. Recent studies have shown that a broad repertoire of tumor‑infiltrating HPV‑specific T-cells is detectable in almost all patients with HPV‑positive tumors. Despite this, there is a development of tumor, which may be facilitated by abnormalities in antigen processing, T-cell dysfunction or prevalence of immunosuppressive cells. Nonetheless, the immunologic profile of HPV‑positive vs. HPV‑negative head and neck squamous cell carcinoma is associated with better outcome, and HPV‑specific immune response is suggested to play an essential role in the better response to conventional therapy of HPV‑positive patients. We also discuss HPV‑specific antitumor immunotherapy approaches, which are now tested in clinical trials. Key words: head and neck cancer – human papillomavirus – immune system – T-lymphocytes – immunotherapy This study was supported by grant Internal Grant Agency of the Czech Ministry of Health No. NT 11542, FH Motol – grant No. 00064203 and by grants SVV 266513, UNCE 204013 and PRVOUK 27-1. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 31. 7. 2015 Accepted: 22. 8. 2015
- MeSH
- Adaptive Immunity MeSH
- Alphapapillomavirus immunology MeSH
- CD4-Positive T-Lymphocytes immunology MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- Immune System Phenomena * MeSH
- Immunotherapy methods MeSH
- Papillomavirus Infections * immunology complications MeSH
- Humans MeSH
- Human papillomavirus 16 immunology MeSH
- Biomarkers, Tumor immunology MeSH
- Head and Neck Neoplasms * genetics immunology therapy MeSH
- Oropharyngeal Neoplasms genetics immunology therapy MeSH
- Prognosis MeSH
- T-Lymphocytes, Regulatory immunology MeSH
- Carcinoma, Squamous Cell genetics immunology therapy MeSH
- T-Lymphocytes immunology MeSH
- Lymphocytes, Tumor-Infiltrating immunology MeSH
- Tumor Escape immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
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 naïve, 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 IFNγ+ 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.
- MeSH
- Programmed Cell Death 1 Receptor * MeSH
- CD8-Positive T-Lymphocytes * immunology MeSH
- Squamous Cell Carcinoma of Head and Neck * etiology immunology MeSH
- Papillomavirus Infections * immunology MeSH
- Humans MeSH
- Head and Neck Neoplasms MeSH
- Lymphocytes, Tumor-Infiltrating MeSH
- Check Tag
- Humans MeSH
