In situ expression of IFN-gamma-inducible T cell alpha chemoattractant in breast cancer mounts an enhanced specific anti-tumor immunity which leads to tumor regression.
Increased evidence indicates that chemokines are involved in tumor growth. ITAC, a key member of chemokines, possesses the ability to recruit T cells and enhance immune responses. Therefore, ITAC might contribute to antitumor immunity. In this study, we evaluated the relationship between the expression of ITAC and human breast cancer advancement. We further investigated whether forced expression of ITAC in tumor sites could mediate enhanced antitumor immunity in a murine breast cancer model. Results showed that ITAC expression level was down-regulated in 31 breast cancer specimens compared to normal mammary tissues, and associated negatively with the stages of breast cancer. Contrarily, forced expression of ITAC in murine 4T1 tumor cells resulted in tumor regression after initial growth upon injection into naïve Balb/c mice. More lymphocytes were recruited to the site of tumor inoculated by 4T1-ITAC and more than 80% of these T cells expressed the ITAC receptor, CXCR3. ITAC-recruited TILs exhibited 4T1-specific proliferation and cytotoxicity, and an increased IFN-gamma but decreased IL-4 production. Importantly, forced expression of ITAC in 4T1 tumor nodules inhibited tumor growth. These findings demonstrated that the decreased expression of ITAC is associated with the advancement of breast cancer in patients. Forced expression of ITAC in tumor site not only induces increased T cell-recruitment and elicits a specific antitumor immunity, but also mediates regression of established 4T1 tumors, indicating the potential application of ITAC-expressing tumor cells in cancer immunotherapy and vaccine designing.
Chu
Yiwei
Y
Department of Immunology of Shanghai Medical College and Institute for Immunobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, Peoples Republic of China.
Yang
Xiuli
X
Xu
Wei
W
Wang
Ying
Y
Guo
Qiang
Q
Xiong
Sidong
S
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D054371:Chemokine CXCL11; D019743:Chemokines, CXC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; D054371:Chemokine CXCL11; D019743:Chemokines, CXC; C515203:Cxcl11 protein, mouse; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine