Transduction of tumor-specific T cells with CXCR2 chemokine receptor improves migration to tumor and antitumor immune responses

Weiyi Peng, Yang Ye, Brian A. Rabinovich, Chengwen Liu, Yanyan Lou, Minying Zhang, Mayra Whittington, Yan Yang, Willem W. Overwijk, Gregory Lizée, Patrick Hwu

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107 Scopus citations

Abstract

Purpose: One of the most important rate-limiting steps in adoptive cell transfer (ACT) is the inefficient migration of T cells to tumors. Because melanomas specifically express the chemokines CXCL1 and CXCL8 that are known to facilitate the CXCR2-dependent migration by monocytes, our aim is to evaluate whether introduction of the CXCR2 gene into tumor-specific T cells could further improve the effectiveness of ACT by enhancing T-cell migration to tumor. Experimental Design: In this study, we used transgenic pmel-1 T cells, which recognize gp100 in the context of H-2Db, that were transduced with luciferase gene to monitor the migration of transferred T cells in vivo. To visualize luciferase-expressing T cells within a tumor, a nonpigmented tumor is required. Therefore, we used the MC38 tumor model, which naturally expresses CXCL1. Results: Mice bearing MC38/gp100 tumor cells treated with CXCR2/luciferase- transduced pmel-1 T cells showed enhanced tumor regression and survival compared with mice receiving control luciferase-transduced pmel-1 T cells. We also observed preferential accumulation of CXCR2-expressing pmel-1 T cells in the tumor sites of these mice using bioluminescence imaging. A similar enhancement in tumor regression and survival was observed when CXCR2-transduced pmel-1 T cells were transferred into mice bearing CXCL1-transduced B16 tumors compared with mice treated with control pmel-1 T cells. Conclusions: These results implicate that the introduction of the CXCR2 gene into tumor-specific T cells can enhance their localization to tumors and improve antitumor immune responses. This strategy may ultimately enable personalization of cancer therapies based on chemokine expression by tumors.

Original languageEnglish (US)
Pages (from-to)5458-5468
Number of pages11
JournalClinical Cancer Research
Volume16
Issue number22
DOIs
StatePublished - Nov 15 2010

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Peng, W., Ye, Y., Rabinovich, B. A., Liu, C., Lou, Y., Zhang, M., Whittington, M., Yang, Y., Overwijk, W. W., Lizée, G., & Hwu, P. (2010). Transduction of tumor-specific T cells with CXCR2 chemokine receptor improves migration to tumor and antitumor immune responses. Clinical Cancer Research, 16(22), 5458-5468. https://doi.org/10.1158/1078-0432.CCR-10-0712