Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells.
Few studies have demonstrated that innate lymphocytes play a major role in preventing spontaneous tumor formation. We evaluated the development of spontaneous tumors in mice lacking beta-2 microglobulin (beta2m; and thus MHC class I, CD1d, and CD16) and/or perforin, since these tumor cells would be expected to activate innate effector cells. Approximately half the cohort of perforin gene-targeted mice succumbed to spontaneous disseminated B cell lymphomas and in mice that also lacked beta2m, the lymphomas developed earlier (by more than 100 d) and with greater incidence (84%). B cell lymphomas from perforin/beta2m gene-targeted mice effectively primed cell-mediated cytotoxicity and perforin, but not IFN-gamma, IL-12, or IL-18, was absolutely essential for tumor rejection. Activated NK1.1+ and gammadeltaTCR+ T cells were abundant at the tumor site, and transplanted tumors were strongly rejected by either, or both, of these cell types. Blockade of a number of different known costimulatory pathways failed to prevent tumor rejection. These results reflect a critical role for NK cells and gammadeltaTCR+ T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition.
Street
Shayna E A
SE
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre (Peter Mac), 8006, Victoria, Australia.
Hayakawa
Yoshihiro
Y
Zhan
Yifan
Y
Lew
Andrew M
AM
MacGregor
Duncan
D
Jamieson
Amanda M
AM
Diefenbach
Andreas
A
Yagita
Hideo
H
Godfrey
Dale I
DI
Smyth
Mark J
MJ
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology; D054353:Perforin; D010537:Peritoneum / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D001613:beta 2-Microglobulin; D054353:Perforin