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Supplement: Immunonutrition: Enhancing Tumoricidal Cell Activity

The Biology of T Cells: What Is the Relationship between T Cells and Cancer? Will an Increased Number and/or Function of T Cells Result in Lower Cancer Incidence?¹

Department of Immunology, The Scripps Research Institute, La Jolla, CA

²To whom correspondence should be addressed. E-mail: havran{at}scripps.edu.

KEY WORDS: • dendritic epithelial T cell • epithelial T cells

T cells are relatively few in number in normal blood and lymphoid organs. In contrast, they are a predominant or even exclusive T cell population in epithelial tissues (1). Several features of the ontogeny, tissue tropism, and antigen-receptor diversity of T cells are very different from T cells that express ß antigen receptors. In addition, T cells can be divided into at least two subtypes, lymphoid and epithelial, with distinct origin, maturation requirements, and functions. Little is known about the antigen specificity and specialized functions of T cell populations, and these are areas of active interest.

Our recent studies on the function of epithelial T cells in the mouse have demonstrated a role for these cells in epithelial homeostasis and tissue repair that is distinct from roles played by lymphoid ß and T cells (2,3). Work from others has shown a role for murine epithelial T cells in regulation of malignancy. Active areas of research include identification of antigens and costimulatory molecules that regulate T cell function. Mouse models of tissue injury, inflammation, and malignancy are being used to investigate the mechanisms of action of T cells and potential modulation of their responses for application to human disease.

Interestingly, T cells are increased in number in a variety of human infectious and noninfectious diseases. In addition, it has been shown that human T cells can exhibit a potent antitumor response in vitro and in vivo (4,5). In recent years several groups have identified small nonpeptidic molecules, including microbial metabolites, alkylamines, and aminobisphosphonates as stimulatory antigens for the major population of circulating human T cells. These compounds have now been used to expand T cells in vitro and in vivo for immune therapy in patients with various malignancies (6). In vitro and animal studies are aimed at identifying the mechanisms of the antitumor responses and to optimize strategies for T cell mediated immunotherapy (7). These results indicate that T cells may be useful for immunotherapy to induce antitumor responses.

FOOTNOTES

¹ Published in a supplement to The Journal of Nutrition. Presented during a workshop entitled: "Immunonutrition: Enhancing Tumoricidal Cell Activity," held in Bethesda, MD, March 23, 2005. This workshop was sponsored by the Division of Cancer Prevention, NCI, NIH, DHHS. Guest editors for the supplement publication were Susan S. Percival, John A. Milner, and Christopher A. Jolly. Guest Editor Disclosure: Susan S. Percival: no relationships to disclose; John A. Milner: no relationships to disclose; Christopher A. Jolly: received reimbursement for travel expenses from NCI.

LITERATURE CITED

1. Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, Hobby P, Sutton B, Tigelaar RE, Hayday AC. Regulation of cutaneous malignancy by T cells. Science. 2001;294:605-609.[Abstract/Free Full Text]

2. Jameson J, Ugarte K, Chen N, Yachi P, Fuchs E, Boismenu R, Havran WL. A role for skin T cells in wound healing. Science. 2002;296:747-749.[Abstract/Free Full Text]

3. Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R. Protection of the intestinal mucosa by intraepithelial T cells. Proc Natl Acad Sci U S A. 2002;99:14338-14343.[Abstract/Free Full Text]

4. Wilhelm M, Kunzmann V, Eckstein S, Reimer P, Weissinger F, Ruediger T, Tony HP. T cells for immune therapy of patients with lymphoid malignancies. Blood. 2003;102:200-206.[Abstract/Free Full Text]

5. Gao Y, Yang W, Pan M, Scully E, Girardi M, Augenlicht LH, Craft J, Yin Z. T cells provide an early source of IFN-g in tumor immunity. J Exp Med. 2003;198:433-442.[Abstract/Free Full Text]

6. Dieli F, Gebbia N, Poccia F, Caccamo N, Montesano C, Fulfaro F, Arcara C, Valerio MR, Meraviglia S, et al. Induction of T lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo. Blood. 2003;102:2310-2311.[Free Full Text]

7. Kabelitz D, Wesch D, Pitters E, Zoller M. Characterization of tumor reactivity of human Vg9Vd2 T cells in vitro and in SCID mice in vivo. J Immunol. 2004;173:6767-6776.[Abstract/Free Full Text]

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