期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 110, 期 2, 页码 185-192出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI200215175
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资金
- NCI NIH HHS [R01 CA083856, CA-83856] Funding Source: Medline
- NIAMS NIH HHS [AR-31203, AR-39555, R01 AR039555, R37 AR039555, R01 AR031203] Funding Source: Medline
- NIA NIH HHS [AG-15061] Funding Source: Medline
Development of tumor immunotherapies focuses on inducing autoimmune responses against tumor-associated self-antigens primarily encoded by normal, unmutated genes. We hypothesized that such responses could be elicited by T cell homeostatic proliferation in the periphery, involving expansion of T cells recognizing self-MHC/peptide ligands. Herein, we demonstrate that sublethally irradiated lymphopenic mice transfused with autologous or syngeneic T cells showed tumor growth inhibition when challenged with melanoma or colon carcinoma cells. importantly, the antitumor response depended on homeostatic expansion of a polyclonal T cell population within lymph nodes. This response was effective even for established tumors, was characterized by CD8(+) T cell-mediated tumor-specific cytotoxicity and IFN-gamma production, and was associated with long-term memory. The results indicate that concomitant induction of the physiologic processes of homeostatic T cell proliferation and tumor antigen presentation in lymph nodes triggers a beneficial antitumor autoimmune response.
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