Tim-3+ T-bet+ tumor-specific Th1 cells colocalize with and inhibit development and growth of murine neoplasms

William J. Simmons, Mythili Koneru, Mani Mohindru, Rajan Thomas, Scott Cutro, Parul Singh, Rosemarie H. DeKruyff, Giorgio Inghirami, Anthony J. Coyle, Byung S. Kim, Nicholas M. Ponzio

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Although T cells infiltrate many types of murine and human neoplasms, in many instances tumor-specific cytotoxicity is not observed. Strategies to stimulate CTL-mediated antitumor immunity have included in vitro stimulation and/or genetic engineering of T cells, followed by adoptive transfer into tumor-bearing hosts. In this model of B cell lymphoma in SJL/J mice, we used Tim-3+ T-bet+ Th1 cells to facilitate the development of tumor-specific CTL. Tumor-specific Th1 cell lines were polarized with IL-12 during in vitro stimulation and long term maintenance. As few as 5 million Tim-3+ T-bet+ Th1 cells enabled recipients to resist growth of malignant transplantable cells. In addition, similar numbers of Th1 cells injected into 2- to 3-mo-old mice inhibited development of the spontaneous primary lymphomas, which normally arise in 90% of aging mice. CFSE+ Th1 cells colocalized with injected tumor cells in vivo and formed conjugates with the tumor cells within follicles, whereas in nontumor-challenged recipients the CFSE+ Th1 cells localized only within the T cell zones of the spleen. These results provide evidence that adoptive immunotherapy with Tim-3+ T-bet+ tumor-specific Th1 cells can be used to induce host cytotoxic responses that inhibit the development and growth of neoplastic cells.

Original languageEnglish (US)
Pages (from-to)1405-1415
Number of pages11
JournalJournal of Immunology
Volume174
Issue number3
DOIs
StatePublished - Feb 1 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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