title: Very Late Antigen-1 Marks Functional Tumor-Resident CD8 T Cells and Correlates with Survival of Melanoma Patients.
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 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+TRMdevelop in murine tumors within 2 weeks, where they exhibit increased activation status, as well as superior effector functions. In addition,in vivoblockade of either VLA-1 or CD103 significantly impaired control of subcutaneous tumors. Together, our data indicate that VLA-1+TRMdevelop in tumors and play an important role in tumor immunity, presenting novel targets for the optimization of cancer immunotherapy.
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Timothy
authors.initials: T
authors.lastname: Murray
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Silvia A
authors.initials: SA
authors.lastname: Fuertes Marraco
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Baumgaertner
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Natacha
authors.initials: N
authors.lastname: Bordry
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Laurène
authors.initials: L
authors.lastname: Cagnon
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Alena
authors.initials: A
authors.lastname: Donda
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Grégory
authors.initials: G
authors.lastname: Verdeil
authors.affiliation: Ludwig Cancer Research, Department of Oncology, University of Lausanne , Lausanne , Switzerland.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
keywords: CD103; VLA-1; cancer vaccines; melanoma; tissue-resident memory T cells