CD103 blockade impair anti-CTLA-4 immunotherapy in oral cancer

CD103⁺CD8⁺T cells is a subtype of T cells with excellent tumor killing ability and it could response to immune checkpoint blockade therapy in several types of cancer, but the phenotype, role and molecular mechanism CD103⁺CD8⁺T cells in the OSCC still unclear.

The distribution and phenotype of CD103⁺CD8⁺T cells were investigated by performing multiplexed immunohistochemistry on human OSCC tissue microarray and flow cytometric analysis of fresh OSCC tumor-infiltrating lymphocytes (TILs). By in vivo use of anti-CD103 monoclonal antibody (mAb) in the 4MOSC1 tumor-bearing mouse model, CD103⁺CD8⁺T cell infiltration and cytotoxicity was clarified.

The majority of CD8⁺T cells in both human and animal OSCC intra-tumoral region were CD103⁺CD8⁺T cells with high expression levels of cytotoxic molecules, which can be impaired by CD103 blockade. In addition, combined use of anti-CD103 mAb with anti-CTLA-4 mAb displayed impaired immune checkpoint blockade therapy efficiency.

CD103⁺CD8⁺T cells are the major intra-tumoral subset of CD8⁺T cells in both animal and human OSCC, and that CD103⁺CD8⁺T cells demonstrate remarkable tumor-infiltrating and tumor-killing properties, thereby CD103⁺CD8⁺T cells may critical for anti-CTLA-4 immunotherapy in OSCC.