, Volume 62, Issue 7, pp 1199-1210

Anti-metastatic potential of human Vδ1+ γδ T cells in an orthotopic mouse xenograft model of colon carcinoma

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Abstract

The role of human intraepithelial Vδ1+ γδ T cell cytotoxic effectors in the immune surveillance against metastatic colon cancer has never been addressed, despite their reported capacity to infiltrate colon carcinomas and to kill colonic cancer cells in vitro. We previously showed that Vδ1+ γδ T cells are enriched in blood in response to cytomegalovirus (CMV) infection, and that such increase may be protective against epithelial cancers. The objective of the present study was to investigate whether CMV-induced Vδ1+ γδ T lymphocytes could inhibit the propagation of human colon tumors in vivo, in order to evaluate their immunotherapeutic potential in this context. Even though metastases are an important cause of death in various cancers including colorectal cancer (CRC), the anti-metastatic effect of immune effectors has been poorly analyzed. To this purpose, we set up a reliable model of metastatic colon cancer through orthotopic implantation of luciferase-expressing human HT29 cells in immunodeficient mice. Using bioluminescence imaging to follow the outcome of colonic cancer cells, we showed that a systemic treatment with CMV-induced Vδ1+ γδ T cells could not only inhibit primary colon tumor growth but also the emergence of secondary tumor foci in the lungs and liver. Finally, our data lead to propose that Vδ1+ γδ T lymphocytes may directly influence the appearance of metastases independently from their control of primary tumor size. These findings, which extend our previous work, pave the road for the potential manipulation of Vδ1+ γδ T lymphocytes in novel anti-CRC immunotherapeutic protocols.