Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 13 - Trang 7556-7561 - 1998
Daniel H. Kaplan1, Vijay Shankaran1, Anand S. Dighe1, Elisabeth Stockert1,2, Michel Aguet1, Lloyd J. Old1,2, Robert D. Schreiber1
1Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110; Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10105; and Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Lausanne, Switzerland
2Ludwig Institute for Cancer Research

Tóm tắt

This study demonstrates that endogenously produced interferon γ (IFN-γ) forms the basis of a tumor surveillance system that controls development of both chemically induced and spontaneously arising tumors in mice. Compared with wild-type mice, mice lacking sensitivity to either IFN-γ (i.e., IFN-γ receptor-deficient mice) or all IFN family members (i.e., Stat1-deficient mice) developed tumors more rapidly and with greater frequency when challenged with different doses of the chemical carcinogen methylcholanthrene. In addition, IFN-γ-insensitive mice developed tumors more rapidly than wild-type mice when bred onto a background deficient in the p53 tumor-suppressor gene. IFN-γ-insensitive p53−/−mice also developed a broader spectrum of tumors compared with mice lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN-γ-insensitive mice, we found IFN-γ’s actions to be mediated at least partly through its direct effects on the tumor cell leading to enhanced tumor cell immunogenicity. The importance and generality of this system is evidenced by the finding that certain types of human tumors become selectively unresponsive to IFN-γ. Thus, IFN-γ forms the basis of an extrinsic tumor-suppressor mechanism in immunocompetent hosts.

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Tài liệu tham khảo

10.1146/annurev.iy.11.040193.003035

10.1146/annurev.immunol.15.1.749

10.1146/annurev.immunol.15.1.563

10.1126/science.8197455

10.1016/S0092-8674(00)81288-X

10.1016/S0092-8674(00)81289-1

10.1126/science.8456300

10.1126/science.8456301

10.1016/S0092-8674(00)81166-6

10.1016/S0092-8674(00)81167-8

10.1056/NEJM199612263352602

10.1056/NEJM199612263352604

10.1093/clinids/24.5.982

10.1016/1074-7613(94)90087-6

10.1073/pnas.89.3.1011

R D Schreiber, L J Hicks, A Celada, N A Buchmeier, P W Gray J Immunol 134, 1609–1618 (1985).

10.1016/S0021-9258(18)55039-0

10.1128/MCB.16.6.3214

10.1016/S0960-9822(00)00002-6

10.1074/jbc.271.44.27954

10.1038/356215a0

10.1038/ng1193-225

Ehrlich P. (1909) Ned. Tijdschr. Geneeskd. 5 (Pt. 1) 273–290.

L Thomas Discussion of Cellular and Humoral Aspects of Hypersensitivity States (Hoeber–Harper, New York), pp. 529–532 (1959).

10.1159/000386035

O Stutman J Natl Cancer Inst 2, 353–358 (1979).

10.1126/science.183.4124.534

10.1146/annurev.iy.12.040194.002005

10.1146/annurev.iy.10.040192.003153

10.1146/annurev.iy.06.040188.002341

10.1084/jem.184.5.1781

10.1073/pnas.91.12.5657

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Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 13

7556-7561

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