Induction of postsurgical tumor immunity and T-cell memory by a poorly immunogenic tumor.
The generation of protective CD8 T-cell memory against tumor-expressed self-antigens is an important but elusive goal of cancer immunotherapy. The possibility that a progressive, poorly immunogenic tumor can induce T-cell memory against self-antigens has not previously been studied. Herein, we report that growth of the poorly immunogenic B16 melanoma in the absence of regulatory T cells (T(reg)) generates CD8 T-cell responses that develop into functional memory after the tumor has been surgically excised. Tumor-primed memory T cells recognized melanocyte differentiation antigens TRP-2/DCT and gp100 and persisted for as long as 5 months following surgical tumor excision. Phenotypic analysis showed that these cells develop into both central and effector memory T-cell subsets, which produce IFN-gamma and interleukin-2 on reencounter with antigen. Most importantly, tumor-primed memory T cells mediated the rejection of intradermal and systemically disseminated challenge tumors given 30 to 60 days following surgery. Tumor-excised mice also developed autoimmune vitiligo, showing that T(reg) cells prevent tissue-specific autoimmunity in tumor-bearing hosts. This study establishes that T(reg) depletion in tumor-bearing hosts drives the natural development of protective T-cell memory. Generating such responses may aid in the clinical management of tumor recurrence and metastasis following surgery.
Zhang
Peisheng
P
Department of Microbiology and Immunology and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Côté
Anik L
AL
de Vries
Victor C
VC
Usherwood
Edward J
EJ
Turk
Mary Jo
MJ
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011184:Postoperative Period; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014820:Vitiligo / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D007371:Interferon-gamma