Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells Journal Article
| Authors: | Turk, M. J.; Guevara-Patiño, J. A.; Rizzuto, G. A.; Engelhorn, M. E.; Houghton, A. N. |
| Article Title: | Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells |
| Abstract: | Concomitant tumor immunity describes immune responses in a host with a progressive tumor that rejects the same tumor at a remote site. In this work, concomitant tumor immunity was investigated in mice bearing poorly immunogenic B16 melanoma. Progression of B16 tumors did not spontaneously elicit concomitant immunity. However, depletion of CD4+ T cells in tumor-bearing mice resulted in CD8+ T cell-mediated rejection of challenge tumors given on day 6. Concomitant immunity was also elicited by treatment with cyclophosphamide or DTA-1 monoclonal antibody against the glucocorticoid-induced tumor necrosis factor receptor. Immunity elicited by B16 melanoma cross-reacted with a distinct syngeneic melanoma, but not with nonmelanoma tumors. Furthermore, CD8+ T cells from mice with concomitant immunity specifically responded to major histocompatibility complex class I-restricted epitopes of two melanocyte differentiation antigens. RAG1-/- mice adoptively transferred with CD8+ and CD4+ T cells lacking the CD4+CD25+ compartment mounted robust concomitant immunity, which was suppressed by readdition of CD4+CD25+ cells. Naturally occurring CD4+CD25+ T cells efficiently suppressed concomitant immunity mediated by previously activated CD8+ T cells, demonstrating that precursor regulatory T cells in naive hosts give rise to effective suppressors. These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor. |
| Keywords: | controlled study; unclassified drug; nonhuman; cd8 antigen; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; melanoma; granulocyte macrophage colony stimulating factor; animal experiment; animal model; cyclophosphamide; cell differentiation; mice, inbred c57bl; monoclonal antibody; immunogenicity; melanoma b16; melanoma, experimental; glucocorticoid; adoptive transfer; tumor immunity; tumor necrosis factor receptor; cd4 antigen; tumor growth; rag1 protein; cross reaction; enzyme linked immunospot assay; tumor rejection; lymphocyte depletion; suppressor cell; helper cell; antigens, differentiation; major histocompatibility antigen class 1; interleukin-10; interleukin 2 receptor; receptors, interleukin-2; granulocyte-macrophage colony-stimulating factor; gitr; immune suppression; genes, rag-1; cancer immunity; male; priority journal; article; melanocyte differentiation antigen; monoclonal antibody dta 1 |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 200 |
| Issue: | 6 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2004-09-20 |
| Start Page: | 771 |
| End Page: | 782 |
| Language: | English |
| DOI: | 10.1084/jem.20041130 |
| PROVIDER: | scopus |
| PMCID: | PMC2211964 |
| PUBMED: | 15381730 |
| DOI/URL: | |
| Notes: | J. Exp. Med. -- Cited By (since 1996):321 -- Export Date: 16 June 2014 -- CODEN: JEMEA -- Source: Scopus |
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