Very Late Antigen-1 Marks Functional Tumor-Resident CD8 T Cells and Correlates with Survival of Melanoma Patients

• Published in: Frontiers in immunology 2016-12, Vol.7, p.573-573
• Main Authors: Murray, Timothy, Fuertes Marraco, Silvia A, Baumgaertner, Petra, Bordry, Natacha, Cagnon, Laurène, Donda, Alena, Romero, Pedro, Verdeil, Grégory, Speiser, Daniel E
• Format: Article
• Language: English
• Subjects: Cancer Vaccines; CD103; Immunology; Melanoma; tissue-resident memory T cells; VLA-1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2016.00573

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 (T ) differentiation. We employed a mouse model of melanoma to further characterize VLA-1-expressing TIL. Our data show that VLA-1 T develop in murine tumors within 2 weeks, where they exhibit increased activation status, as well as superior effector functions. In addition, blockade of either VLA-1 or CD103 significantly impaired control of subcutaneous tumors. Together, our data indicate that VLA-1 T develop in tumors and play an important role in tumor immunity, presenting novel targets for the optimization of cancer immunotherapy.