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

Details

Serval ID
serval:BIB_C2BA1FEE13FC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Very Late Antigen-1 Marks Functional Tumor-Resident CD8 T Cells and Correlates with Survival of Melanoma Patients.
Journal
Frontiers in immunology
Author(s)
Murray T., Fuertes Marraco S.A., Baumgaertner P., Bordry N., Cagnon L., Donda A., Romero P., Verdeil G., Speiser D.E.
ISSN-L
1664-3224
Publication state
Published
Issued date
2016
Volume
7
Pages
573
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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(+) 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.
Pubmed
Open Access
Yes
Create date
10/02/2017 10:56
Last modification date
20/07/2020 5:26
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