IADR Abstract Archives
Specific Blockade CD73 Alters the Exhausted T Cells in HNSCC
Objectives: 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.
Nevertheless, whether CD73 blockade reverses the immunosuppression and constitutes an effective therapeutic target in HNSCC remains to be shown.
Methods: Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model and in vivo treatment with anti-CD73 monoclonal antibody (mAb). Analysed by flow cytometry, in additon, the human tissue microarrays showed the expression of CD73 in HNSCC.
Results: the expression of CD73 on T cells represents an ‘exhausted’ phenotype in competent HSNCC mouse model. Furthermore, in vivo assay showed the blockade of CD73 restrains tumor progression and reverses a large part of ‘exhausted’ CD4+ and CD8+ T cells to immune-competent. Moreover, we showed a potential resistant population remaining CD73 positive during the anti-CD73 treatment. The human tumor samples reveal that CD73 is overexpressed in tumor-infiltrating immune cells, and the positive expression of CD73 is correlated with the poor prognosis in human HNSCC.
Conclusions: 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.
Nevertheless, whether CD73 blockade reverses the immunosuppression and constitutes an effective therapeutic target in HNSCC remains to be shown.
Methods: Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model and in vivo treatment with anti-CD73 monoclonal antibody (mAb). Analysed by flow cytometry, in additon, the human tissue microarrays showed the expression of CD73 in HNSCC.
Results: the expression of CD73 on T cells represents an ‘exhausted’ phenotype in competent HSNCC mouse model. Furthermore, in vivo assay showed the blockade of CD73 restrains tumor progression and reverses a large part of ‘exhausted’ CD4+ and CD8+ T cells to immune-competent. Moreover, we showed a potential resistant population remaining CD73 positive during the anti-CD73 treatment. The human tumor samples reveal that CD73 is overexpressed in tumor-infiltrating immune cells, and the positive expression of CD73 is correlated with the poor prognosis in human HNSCC.
Conclusions: 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.