T cell-mediated help against tumors.
Adoptive transfer of tumor antigen-specific T helper (Th) cells is a surprisingly potent anti-tumor therapy. Even in RIP1-Tag2 mice with a rapidly growing, aggressive endogenous beta cell tumor Th can significantly extend life time and are more efficient than any other therapy studied. The therapeutic effect of Th cells seems to be independent of tumor cell destruction. It critically relies on three principles: (1) inhibition of tumor angiogenesis, (2) inhibition of beta cell proliferation, and (3) induction of tumor dormancy. As tumor cell destruction by cytotoxic CD8(+) T cells (CTL) largely failed in tumor therapy, induction of tumor dormancy by Th cell-mediated immune responses represents a novel therapeutic option that may be combined with other cytotoxic regimens, e.g., radio- and/or chemotherapy, as it is established for bone marrow transplantation. Importantly, Th cell efficacy strictly requires interferon gamma (IFNgamma) signaling, and in the absence of IFNgamma, Th cells may even worsen tumor diseases. Therefore, using the immune system to control tumor dormancy represents a novel approach, especially as therapy of tumors resistant to conventional therapies. Yet, it is important to underline that Th cell-based antitumor effects critically depend on a functional cytokine network, especially appropriate IFNgamma signaling.
Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
Thomas
T
Wieder
Heidi
H
Braumüller
Manfred
M
Kneilling
Bernd
B
Pichler
Martin
M
Röcken
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D020690:GTPase-Activating Proteins; C490620:Ralbp1 protein, mouse; D007371:Interferon-gamma