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.