Title | Tim-3+ T-bet+ tumor-specific Th1 cells colocalize with and inhibit development and growth of murine neoplasms. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Simmons WJ, Koneru M, Mohindru M, Thomas R, Cutro S, Singh P, Dekruyff RH, Inghirami G, Coyle AJ, Kim BS, Ponzio NM |
Journal | J Immunol |
Volume | 174 |
Issue | 3 |
Pagination | 1405-15 |
Date Published | 2005 Feb 01 |
ISSN | 0022-1767 |
Keywords | Adoptive Transfer, Animals, Cell Differentiation, Cell Division, Cell Line, Tumor, Cell Proliferation, Coculture Techniques, DNA-Binding Proteins, Epitopes, T-Lymphocyte, Hepatitis A Virus Cellular Receptor 2, Interleukin-12, Lymphocytes, Tumor-Infiltrating, Lymphoma, B-Cell, Mice, Neoplasm Transplantation, NFATC Transcription Factors, Nuclear Proteins, Receptors, Virus, T-Box Domain Proteins, T-Lymphocytes, Cytotoxic, Th1 Cells, Transcription Factors |
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. |
DOI | 10.4049/jimmunol.174.3.1405 |
Alternate Journal | J Immunol |
PubMed ID | 15661898 |
Related Faculty:
Giorgio Inghirami, M.D.