Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients
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...
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doaj-d25e612022ab4b5d83d3a732e5cee8942020-11-25T02:04:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-12-01710.3389/fimmu.2016.00573236926Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patientsTimothy Murray0Silvia A Fuertes Marraco1Petra Baumgaertner2Natacha Bordry3Laurène Cagnon4Alena Donda5Pedro Romero6Grégory Verdeil7Daniel E. Speiser8University of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneA 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 (TIL) are highly enriched in melanoma metastases in diverse tissues. VLA-1-expressing TIL frequently coexpress CD69 and CD103, indicating tissue resident memory cell (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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00573/fullCancer VaccinesMelanomaCD103tissue-resident memory T cellsVLA-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Timothy Murray Silvia A Fuertes Marraco Petra Baumgaertner Natacha Bordry Laurène Cagnon Alena Donda Pedro Romero Grégory Verdeil Daniel E. Speiser |
spellingShingle |
Timothy Murray Silvia A Fuertes Marraco Petra Baumgaertner Natacha Bordry Laurène Cagnon Alena Donda Pedro Romero Grégory Verdeil Daniel E. Speiser Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients Frontiers in Immunology Cancer Vaccines Melanoma CD103 tissue-resident memory T cells VLA-1 |
author_facet |
Timothy Murray Silvia A Fuertes Marraco Petra Baumgaertner Natacha Bordry Laurène Cagnon Alena Donda Pedro Romero Grégory Verdeil Daniel E. Speiser |
author_sort |
Timothy Murray |
title |
Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients |
title_short |
Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients |
title_full |
Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients |
title_fullStr |
Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients |
title_full_unstemmed |
Very Late Antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients |
title_sort |
very late antigen-1 marks functional tumor-resident cd8 t cells and correlates with survival of melanoma patients |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2016-12-01 |
description |
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 (TIL) are highly enriched in melanoma metastases in diverse tissues. VLA-1-expressing TIL frequently coexpress CD69 and CD103, indicating tissue resident memory cell (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. |
topic |
Cancer Vaccines Melanoma CD103 tissue-resident memory T cells VLA-1 |
url |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00573/full |
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