TY - JOUR AU - Murray, Timothy AU - Fuertes Marraco, Silvia A. AU - Baumgaertner, Petra AU - Bordry, Natacha AU - Cagnon, Laurène AU - Donda, Alena AU - Romero, Pedro AU - Verdeil, Grégory AU - Speiser, Daniel E. PY - 2016 M3 - Original Research TI - Very Late Antigen-1 Marks Functional Tumor-Resident CD8 T Cells and Correlates with Survival of Melanoma Patients JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2016.00573 VL - 7 SN - 1664-3224 N2 - A major limiting factor in the success of immunotherapy is tumor infiltration by CD8+ T cells, a process that remains poorly understood. In the present study, we characterized homing receptors expressed by human melanoma-specific CD8+ T cells. Our data reveal that P-selectin binding and expression of the retention integrin, very late antigen (VLA)-1, by vaccine-induced T cells correlate with longer patient survival. Furthermore, we demonstrate that CD8+VLA-1+ tumor-infiltrating lymphocytes (TILs) are highly enriched in melanoma metastases in diverse tissues. VLA-1-expressing TIL frequently co-express CD69 and CD103, indicating tissue-resident memory T cells (TRM) differentiation. We employed a mouse model of melanoma to further characterize VLA-1-expressing TIL. Our data show that VLA-1+ TRM develop in murine tumors within 2 weeks, where they exhibit increased activation status, as well as superior effector functions. In addition, in vivo blockade of either VLA-1 or CD103 significantly impaired control of subcutaneous tumors. Together, our data indicate that VLA-1+ TRM develop in tumors and play an important role in tumor immunity, presenting novel targets for the optimization of cancer immunotherapy. ER -