TY - JOUR
T1 - Modeling anti-tumor Th1 and Th2 immunity in the rejection of melanoma
AU - Eftimie, Raluca
AU - Bramson, Jonathan L.
AU - Earn, David J. D.
PY - 2010/8/7
Y1 - 2010/8/7
N2 - Recent experiments indicate that CD4(+) Th2 cells can reject skin tumors in mice, while CD4(+) Th1 cells cannot (Mattes et al., 2003; Zhang et al., 2009). These results are surprising because CD4(+) Th1 cells are typically considered to be capable of tumor rejection. We used mathematical models to investigate this unexpected outcome. We found that neither CD4(+) Th1 nor CD4(+) Th2 cells could eliminate the cancer cells when acting alone, but that tumor elimination could be induced by recruitment of eosinophils by the Th2 cells. These recruited eosinophils had unexpected indirect effects on the decay rate of type 2 cytokines and the rate at which Th2 cells are inactivated through interactions with cancer cells. Strikingly, the presence of eosinophils impacted tumor growth more significantly than the release of tumor-suppressing cytokines such as IFN-gamma and TNF-alpha. Our simulations suggest that novel strategies to enhance eosinophil recruitment into skin tumors may improve cancer immunotherapies. (C) 2010 Elsevier Ltd. All rights reserved.
AB - Recent experiments indicate that CD4(+) Th2 cells can reject skin tumors in mice, while CD4(+) Th1 cells cannot (Mattes et al., 2003; Zhang et al., 2009). These results are surprising because CD4(+) Th1 cells are typically considered to be capable of tumor rejection. We used mathematical models to investigate this unexpected outcome. We found that neither CD4(+) Th1 nor CD4(+) Th2 cells could eliminate the cancer cells when acting alone, but that tumor elimination could be induced by recruitment of eosinophils by the Th2 cells. These recruited eosinophils had unexpected indirect effects on the decay rate of type 2 cytokines and the rate at which Th2 cells are inactivated through interactions with cancer cells. Strikingly, the presence of eosinophils impacted tumor growth more significantly than the release of tumor-suppressing cytokines such as IFN-gamma and TNF-alpha. Our simulations suggest that novel strategies to enhance eosinophil recruitment into skin tumors may improve cancer immunotherapies. (C) 2010 Elsevier Ltd. All rights reserved.
U2 - 10.1016/j.jtbi.2010.04.030
DO - 10.1016/j.jtbi.2010.04.030
M3 - Article
C2 - 20450922
SN - 0022-5193
VL - 265
SP - 467
EP - 480
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
IS - 3
ER -