Matrix metalloproteinase-23 as a new immunotherapeutic checkpoint target in melanoma.

3030 Background: Matrix metalloproteinase-23 (MMP-23) can inhibit T cell activation by selectively blocking the voltage-gated potassium channel Kv1.3, and may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma. Methods: We characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the intrinsic anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T-cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression. Results: Our data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T-cell resp...