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Prognostic value of arginase‐II expression and regulatory T‐cell infiltration in head and neck squamous cell carcinoma
Author(s) -
Bron Luc,
Jandus Camilla,
AndrejevicBlant Snezana,
Speiser Daniel E.,
Monnier Philippe,
Romero Pedro,
Rivals JeanPaul
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27728
Subject(s) - foxp3 , cancer research , head and neck squamous cell carcinoma , medicine , stromal cell , arginase , immune system , pathology , cd11c , head and neck cancer , cancer , biology , immunology , biochemistry , amino acid , arginine , gene , phenotype
Tumor‐infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3 + T cells, and relatively high levels of BDCA2 + and FOXP3 + cells in stromal (peripheral) regions of the tumors. Tumor‐infiltrating (intraepithelial) FOXP3 + T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase‐II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase‐2 by 43%, and B‐cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c + myeloid dendritic cells, and high numbers of FOXP3 + T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease‐free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.