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 Blood, 1 January 2007, Vol. 109, No. 1, pp. 253-258.
Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-01-031278.

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IMMUNOBIOLOGY

Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice

Kenneth F. May, Jr1, Kenneth Lute1, Ergun Kocak1, Shahab Abdessalam1, Lijie Yin1, Ou Li1, Zhen Guan2, Gary Philips3, Pan Zheng1, and Yang Liu1,

1 Division of Cancer Immunology, Department of Pathology; 2 Department of Physiology; and 3 Center for Biostatistics, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus

The impact of timing of antigen introduction into fetus and neonates leads to the suggestion that pre-existing antigens are tolerogenic to immunocompetent cells generated thereafter. This hypothesis predicts that in patients with cancer who are undergoing bone marrow transplantation, newly produced T cells with specificity for pre-existing tumor cells will be inactivated by the tumor antigens in the host. Because the effect of tumor cells on developing cancer-reactive T cells has not been investigated, we set out to systematically analyze the impact of tumor cells in the periphery on the development of tumor-reactive T cells in the thymus and their immunocompetence in the periphery. Our data demonstrate that in the host in which a tumor is established in the periphery, the cancer-reactive T cells develop normally, remain fully immunocompetent, become activated in the periphery, and cause regression of large established tumors. The immunocompetence of T cells generated in an antigen-bearing host is also confirmed in a skin graft transplantation model.


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