Unmasking immunosurveillance against a syngeneic colon cancer by elimination of CD4+ NKT regulatory cells and IL‐13

JM Park, M Terabe, LT van den Broeke… - … journal of cancer, 2005 - Wiley Online Library
JM Park, M Terabe, LT van den Broeke, DD Donaldson, JA Berzofsky
International journal of cancer, 2005Wiley Online Library
We have previously observed a novel role of natural killer T (NKT) cells in negative
regulation of antitumor immune responses against an immunogenic regressor tumor
expressing a transfected viral antigen. Here, we investigated whether hidden spontaneous
antitumor immunosurveillance, in the absence of a vaccine, could be revealed by disruption
of this negative regulatory pathway involving CD4+ NKT cells and interleukin‐13 (IL‐13), in
a murine pulmonary metastasis model of a nontransfected, nonregressor, syngeneic tumor …
Abstract
We have previously observed a novel role of natural killer T (NKT) cells in negative regulation of antitumor immune responses against an immunogenic regressor tumor expressing a transfected viral antigen. Here, we investigated whether hidden spontaneous antitumor immunosurveillance, in the absence of a vaccine, could be revealed by disruption of this negative regulatory pathway involving CD4+ NKT cells and interleukin‐13 (IL‐13), in a murine pulmonary metastasis model of a nontransfected, nonregressor, syngeneic tumor, the CT26 colon carcinoma. Lung metastases of CT26 were decreased in CD4+ T cell–depleted BALB/c mice, suggesting that CD4+ T cells were involved in negative regulation of antitumor responses. CD1‐knock out (CD1‐KO) mice, which have conventional CD4+ T cells and CD4+CD25+ regulatory T cells but lack CD1‐restricted CD4+ NKT cells, were significantly resistant to lung metastasis of CT26. The metastases were not further decreased in CD4+ T cell–depleted CD1‐KO mice, implying that CD4+ NKT cells might be the primary negative regulator of antitumor immune responses in BALB/c mice. CD8+ T cells were found to act as effectors in antitumor immune responses, since the inhibition of lung metastases observed in naļve CD1‐KO or CD4+ T cell–depleted mice was abrogated by depletion of CD8+ T cells. Lung metastases were significantly decreased by treatment of mice with an IL‐13 inhibitor, but not by deficiency or inhibition of IL‐4. Thus, even for a nonregressor tumor, immunosurveillance exists but is negatively regulated via CD4+ NKT cells possibly mediated by IL‐13, and can be unmasked by removal of these negative regulatory components. Published © 2004 Wiley‐Liss, Inc.
Wiley Online Library