Major histocompatibility complex class I and unique antigen expression by murine tumors that escaped from CD8+ T-cell-dependent surveillance.
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.
Ward
P L
PL
Department of Pathology, University of Chicago, Illinois 60637.
Koeppen
H K
HK
Hurteau
T
T
Rowley
D A
DA
Schreiber
H
H
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology*; D016827:CD8 Antigens; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D007111:Immunity, Cellular; D007157:Immunologic Surveillance; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens