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

Jessica J. O'Konek, Elena Ambrosino, Anja C. Bloom, Lise Pasquet, Chandirasegaran Massilamany, Zheng Xia, Masaki Terabe*, Jay A. Berzofsky*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)


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.
Original languageEnglish
Article numbere1439305
Number of pages9
Issue number7
Publication statusPublished - 1 Jan 2018


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

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