Systemic and local human papillomavirus 16-specific T-cell immunity in patients with head and neck cancer.
Squamous cell carcinomas of the head and neck (HNSCC), in particular those of the oropharynx, can be caused by human papilloma virus Type 16 (HPV16). Whereas these HPV-induced oropharyngeal carcinomas may express the HPV16 E6 and E7 oncoproteins and are associated with better survival, the nonvirally induced HNSCC are associated with overexpression of p53. In this study we assessed the presence of systemic and local T cells reactive against these oncoproteins in HNSCC. An exploratory study on the presence, type and function of HPV16- and/or p53-specific T cells in the blood, tumor and/or metastatic lymph node as measured by several immune assays was performed in an unselected group of 50 patients with HNSCC. Tumor tissue was tested for HPV DNA and the overexpression of p53 protein. Almost all HPV16+ tumors were located in the oropharynx. Circulating HPV16- and p53-specific T cells were found in 17/47 and 7/45 tested patients. T cells were isolated from tumor cultures and/or lymph nodes of 20 patients. HPV16-specific T cells were detected in six of eight HPV+ tumors, but in none of the 12 HPV-tumors. Tumor-infiltrating p53-specific T cells were not detected. In depth analysis of the HPV16-specific T-cell response revealed that this response comprised a broad repertoire of CD4+ T-helper Type 1 and 2 cells, CD4+ regulatory T cells and CD8+ T cells reactive to HPV16. The local presence of HPV16-specific T-cell immunity in HPV16-induced HNSCC implicates a role in the antitumor response and support the development of immunotherapy for HNSCC.
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
M
M
Heusinkveld
R
R
Goedemans
R J P
RJ
Briet
H
H
Gelderblom
J W R
JW
Nortier
A
A
Gorter
V T H B M
VT
Smit
A P M
AP
Langeveld
J C
JC
Jansen
S H
SH
van der Burg
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000821:virology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D009959:Oropharyngeal Neoplasms / Q000276:immunology* / Q000821:virology; D009960:Oropharynx / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000276:immunology / Q000821:virology; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000276:immunology
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53