The tumor barrier comprised of nonantigenic stromal cells may contribute to the failure of tumor rejection. The tumor-necrosis factor superfamily member LIGHT (also known as TNFSF-14) is a ligand of stromal cell–expressed lymphotoxin-β receptor and T cell–expressed herpes viral entry mediator (HVEM). Here we show that forced expression of LIGHT in the tumor environment induces a massive infiltration of naive T lymphocytes that correlates with an upregulation of both chemokine production and expression of adhesion molecules. Activation of these infiltrating T cells, possibly through HVEM, leads to the rejection of established, highly progressive tumors at local and distal sites. Our study indicates that targeting the tumor barrier may be an effective strategy for cancer immunotherapy.
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We thank L. Chen for advice and support, and M. Spiotto and J. Lo for their technical assistance. This work was supported by grants from the NIH (R01-HD37104, R01-DK58897 and P01-CA09296-01). P.Y. is a recipient of an NIH training grant (5T32DK07074).
The authors declare no competing financial interests.
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Yu, P., Lee, Y., Liu, W. et al. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat Immunol 5, 141–149 (2004). https://doi.org/10.1038/ni1029
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