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 repor...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2007-07, Vol.67 (13), p.6468-6476
Main Authors: PEISHENG ZHANG, COTE, Anik L, DE VRIES, Victor C, USHERWOOD, Edward J, TURK, Mary Jo
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Autoimmune Diseases - immunology
Biological and medical sciences
CD4-Positive T-Lymphocytes - metabolism
Cytokines - metabolism
Immunologic Memory
Immunotherapy - methods
Interferon-gamma - metabolism
Interleukin-2 - metabolism
Male
Medical sciences
Melanoma, Experimental - immunology
Melanoma, Experimental - pathology
Mice
Mice, Inbred C57BL
Pharmacology. Drug treatments
Postoperative Period
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tumors
Vitiligo - immunology
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-07-1264