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Frontiers in immunology
2016;7 573.

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

Timothy Murray, Silvia A Fuertes Marraco, Petra Baumgaertner, Natacha Bordry, Laurène Cagnon, Alena Donda, Pedro Romero, Grégory Verdeil, Daniel E Speiser
Author Information
  1. Timothy Murray: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  2. Silvia A Fuertes Marraco: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  3. Petra Baumgaertner: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  4. Natacha Bordry: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  5. Laurène Cagnon: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  6. Alena Donda: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  7. Pedro Romero: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  8. Grégory Verdeil: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
  9. Daniel E Speiser: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
PMID: 28018343 DOI: 10.3389/fimmu.2016.00573

Abstract

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 CD8VLA-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.

Keywords

CD103 VLA-1 cancer vaccines melanoma tissue-resident memory T cells

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