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Publication : IFNγ-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin.

First Author  Lane RS Year  2018
Journal  J Exp Med Volume  215
Issue  12 Pages  3057-3074
PubMed ID  30381467 Mgi Jnum  J:269872
Mgi Id  MGI:6273111 Doi  10.1084/jem.20180654
Citation  Lane RS, et al. (2018) IFNgamma-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin. J Exp Med 215(12):3057-3074
abstractText  Mechanisms of immune suppression in peripheral tissues counteract protective immunity to prevent immunopathology and are coopted by tumors for immune evasion. While lymphatic vessels facilitate T cell priming, they also exert immune suppressive effects in lymph nodes at steady-state. Therefore, we hypothesized that peripheral lymphatic vessels acquire suppressive mechanisms to limit local effector CD8(+) T cell accumulation in murine skin. We demonstrate that nonhematopoietic PD-L1 is largely expressed by lymphatic and blood endothelial cells and limits CD8(+) T cell accumulation in tumor microenvironments. IFNgamma produced by tissue-infiltrating, antigen-specific CD8(+) T cells, which are in close proximity to tumor-associated lymphatic vessels, is sufficient to induce lymphatic vessel PD-L1 expression. Disruption of IFNgamma-dependent crosstalk through lymphatic-specific loss of IFNgammaR boosts T cell accumulation in infected and malignant skin leading to increased viral pathology and tumor control, respectively. Consequently, we identify IFNgammaR as an immunological switch in lymphatic vessels that balances protective immunity and immunopathology leading to adaptive immune resistance in melanoma.
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