Journal
FRONTIERS IN IMMUNOLOGY
Volume 7, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2016.00573
Keywords
VLA-1; CD103; tissue-resident memory T cells; cancer vaccines; melanoma
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Funding
- Cancer Research Institute (CLIP grant) (NY, USA)
- Ludwig Cancer Research Center (NY, USA)
- Cancer Vaccine Collaborative (NY, USA)
- Swiss National Science Foundation [CRSII3_141879, CRSII3_160708, 320030_152856]
- Wilhelm Sander-Stiftung (Germany)
- Alfred and Annemarie von Sick Foundation
- Swiss Cancer League [3507-08-2014]
- Swiss National Science Foundation (SNF) [CRSII3_160708, 320030_152856, CRSII3_141879] Funding Source: Swiss National Science Foundation (SNF)
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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-RM) differentiation. We employed a mouse model of melanoma to further characterize VLA-1-expressing TIL. Our data show that VLA-1+ T-RM 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(+) T-RM develop in tumors and play an important role in tumor immunity, presenting novel targets for the optimization of cancer immunotherapy.
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