Cancer Immunity 1:5 (2001)

Identification of a tumor-associated contact-dependent activity which reversibly downregulates cytolytic function of CD8+ T cells

Daniel L. Levey¹, Heiichiro Udono², Michael Heike³, and Pramod K. Srivastava⁴

¹Present address: Antigenics Inc., 630 Fifth Avenue, Suite 2100, New York City, NY 10111
²Present address: Department of Medical Zoology and Immunology, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
³Present address: I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Langenbeckstrasse 1, D-55101 Mainz, Germany
⁴Center for Immunotherapy of Cancer and Infectious Diseases, Mail Code 1601, University of Connecticut School of Medicine, Farmington, CT 06030

Keywords: Tumor escape, cytotoxic T lymphocytes, immunologic factors, mice, cultured tumor cells

Abstract

Tumors elicit an immune response in hosts and yet, paradoxically, often grow progressively with fatal consequences. This phenomenon has been attributed to the possible expression by tumor cells of immunomodulatory factors that overcome the anti-tumor effector functions of both specific and non-specific immune cells. This study reports on the ability of the methylcholanthrene-induced fibrosarcoma, Meth A, as well as other tumors of varied histological origins to downregulate the lytic activity of CD8+ T cells. The suppressive activity is contact-dependent and reversible. As tumor-bearing hosts are rarely immunosuppressed systemically, these findings may explain how local events within the tumor bed subvert the specific anti-tumor immune response.