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Major Histocompatibility Complex Class I and Unique Antigen Expression by Murine Tumors That Escaped from CD8⁺ T-Cell-dependent Surveillance¹

Department of Pathology, The University of Chicago, Chicago, Illinois 60637

The rejection of murine UV-induced skin cancers by normal mice is a striking example of powerful immune surveillance of the normal host against malignant cells. In this study, we show that UV-induced regressor tumors regularly grew progressively and killed mice that were depleted of CD8⁺ T-cells. Depletion of CD4⁺ T-cells had no effect, suggesting that CD8⁺ but not CD4⁺ T-cells were required for this immune surveillance. To determine whether change in major histocompatibility complex (MHC) class I expression was a frequent event that caused low immunogenicity of tumors or facilitated escape from immune destruction, recently isolated murine tumors of varying degrees of immunogenicity, including highly immunogenic UV-induced regressor, less immunogenic UV-induced progressor, and poorly immunogenic spontaneous progressor tumors, were compared. There was no correlation between the ability of a tumor to grow progressively in a normal immunocompetent host and the level of constitutive class I expression or the level of expression induced in vitro by interferon. (Only 1 of more than 20 progressor tumors analyzed showed complete loss of a MHC class I molecule.) Some progressor variants showed loss of a unique tumor-specific cytotoxic T-lymphocyte-defined antigen, consistent with earlier evidence of antigen loss providing a mechanism for tumor escape. However, most of the host-selected progressor variants retained both MHC class I antigens and the unique tumor antigens that we could detect with cytotoxic T-lymphocyte clones, suggesting that mechanisms other than loss of MHC class I or of the unique target antigen may be involved in escape of some tumors from a highly effective CD8-dependent host surveillance.

¹ This work was supported by grants from the NIH, RO1 CA-37156, PO1 CA-19266, and R37 CA-22677, and a gift from the Passis family.

² Supported in part by Grant T32 AI-07090. To whom requests for reprints should be addressed, at Department of Pathology, The University of Chicago, 5841 S. Maryland Ave., Box 414, Chicago, IL 60637.

Received 12/19/89.

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