Major histocompatibility complex class I and unique antigen expression by murine tumors that escaped from CD8+ T-cell-dependent surveillance

• Published in: Cancer research (Chicago, Ill.) Vol. 50; no. 13; p. 3851
• Main Authors: Ward, P L, Koeppen, H K, Hurteau, T, Rowley, D A, Schreiber, H
• Format: Journal Article
• Language: English
• Published: United States 01.07.1990
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - analysis; Antigens, Differentiation, T-Lymphocyte - immunology; CD4 Antigens - analysis; CD4 Antigens - immunology; CD8 Antigens; Female; Graft Rejection - immunology; Immunity, Cellular; Immunologic Surveillance; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Mice, Nude; Neoplasm Transplantation; Neoplasms, Radiation-Induced - immunology; T-Lymphocytes - immunology; Transplantation Immunology
• ISSN: 0008-5472

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 gamma 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.