Wolfgang Dummer, Andreas G. Niethammer, Roberto Baccala, Brian R. Lawson, Norbert Wagner, Ralph A. Reisfeld, Argyrios N. Theofilopoulos
J Clin Invest.
2002;
110(2):185–192
doi:10.1172/JCI15175
This article Copyright © 2002, The American Society for Clinical Investigation
Abstract
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D
evelopment 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-γ 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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