In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 138.2-138.2
Abstract:
Non-recirculating tissue-resident memory T (TRM) cells reside permanently in epithelial tissues where they are known to protect against infection. TRM cells have now been identified in various human cancers where they correlate with improved patient outcomes, but the mechanisms through which they may mediate protective tumour immunity remain unclear. Using a novel mouse model of transplantable cutaneous melanoma, we show that tumour-specific TRM cells form spontaneously in the epithelial tumour microenvironment where they protect against cancer development independently of circulating memory T cells. A proportion of epicutaneously inoculated mice remained free of macroscopic tumours long after inoculation, and intravital imaging revealed that these mice harboured dormant melanoma cells in their skin that were dynamically surveyed by tumour-specific TRM cells. Depletion of TRM cells from these mice triggered melanoma escape, indicating that TRM cells suppress tumour progression by promoting cancer-immune equilibrium. Further, we found that pre-activated T cells transferred to tumour-bearing mice in a model of adoptive cell therapy gave rise to TRM cells that inhibited the growth of established melanoma. These tumour-specific TRM cells retained their capacity to execute effector functions and protect against tumour growth despite expression of various inhibitory molecules typically associated with T cell dysfunction. Combined, our findings reveal TRM cells to be durable mediators of anti-tumour immunity and suggest that targeting TRM cell responses could serve as a novel immunotherapeutic strategy to drive elimination of solid tumours.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.138.2
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
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