Differential Regulation of T-cell mediated anti-tumor memory and cross-protection against the same tumor in lungs versus skin

ABSTRACT

A major advantage of immunotherapy of cancer is that effector cells induced at one site should be able to kill metastatic cancer cells in other sites or tissues. However, different tissues have unique immune components, and very little is known about whether effector T cells induced against tumors in one tissue can work against the same tumors in other tissues. Here, we used CT26 murine tumor models to investigate anti-tumor immune responses in the skin and lungs and characterized cross-protection between the two tissues. Blockade of the function of Treg cells with anti-CD25 allowed for T cell-dependent rejection of s.c. tumors. When these mice were simultaneously inoculated i.v. with CT26, they also rejected tumors in the lung. Interestingly, in the absence of s.c. tumors, anti-CD25 treatment alone had no effect on lung tumor growth. These observations suggested that T cell-mediated anti-tumor protective immunity induced against s.c. tumors can also protect against lung metastases of the same tumors. In contrast, NKT cell-deficiency in CD1d^−/− mice conferred significant protection against lung tumors but had no effect on the growth of tumors in the skin, and tumor rejection induced against the CT26 in the lung did not confer protection for the same tumor cells in the skin. Thus, effector cells against the same tumor do not work in all tissues, and the induction site of the effector T cells is critical to control metastasis. Further, the regulation of tumor immunity may be different for the same tumor in different anatomical locations.

KEYWORDS:

• cross-protection
• Immunoregulation
• lung metastases
• NKT cells
• skin tumors
• T-cell immunity
• tissue-specific immunity
• Treg cells

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thanks Amy James for assistance with mouse breeding, the NIH tetramer facility, the Vaccine Branch FACS core facility, the NCI animal facility and Lisa Smith for secretarial help.

Additional information

Funding

This work was supported by the Gui Foundation This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (Z01-C-004020) and by the Gui Foundation.