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Specific blockade CD 73 alters the “exhausted” phenotype of T cells in head and neck squamous cell carcinoma
Author(s) -
Deng WeiWei,
Li YiCun,
Ma SiRui,
Mao Liang,
Yu GuangTao,
Bu LinLin,
Kulkarni Ashok B.,
Zhang WenFeng,
Sun ZhiJun
Publication year - 2018
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.31534
Subject(s) - head and neck squamous cell carcinoma , immunosurveillance , immune system , cancer research , downregulation and upregulation , cd8 , cytotoxic t cell , immunotherapy , 5' nucleotidase , antibody , biology , immunology , adenosine , medicine , cancer , head and neck cancer , endocrinology , in vitro , biochemistry , gene
The adenosine‐induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto‐5‐nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4 + and CD8 + T cells was associated with an “exhausted” phenotype. Further, treatment with anti‐CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the “exhausted” phenotype of CD4 + and CD8 + T cells through downregulation of total expression of PD‐1 and CTLA‐4 on T cells. Whereas the population of CD4 + CD73 hi /CD8 + CD73 hi T cells expressed higher CTLA‐4 and PD‐1 as compared to untreated controls. In addition, the human tissue microarrays showed the expression of CD73 is upregulated on tumor infiltrating immune cells in patients with primary HNSCC. Moreover, CD73 expression is an independent prognostic factor for poor outcome in our cohort of HNSCC patients. Altogether, these findings highlight the immunoregulatory role of CD73 in the development of HNSCC and we propose that CD73 may prove to be a promising immunotherapeutic target for the treatment of HNSCC.