Reduced tumorigenicity of murine tumor cells secreting gamma-interferon is due to nonspecific host responses and is unrelated to class I major histocompatibility complex expression.
Spontaneous SP1 murine adenocarcinoma cells transfected with the murine gamma-interferon (IFN-gamma) gene expressed IFN-gamma (SP1/IFN-gamma) failed to grow in syngeneic hosts and grew in nude mice. The rejection of SP1/IFN-gamma cells was related to the amount of IFN-gamma produced and appeared to be mediated primarily by nonspecific cellular mechanisms, although some role for T-cells in the afferent arm of this response is possible. SP1 cells are H2-Kk negative but express class I antigens when producing IFN-gamma. However, class I major histocompatibility complex (MHC) expression, while likely necessary, was insufficient in itself to prevent tumor growth since secretion of greater than 64 units/ml IFN-gamma was needed to inhibit tumorigenicity while only 8 units/ml IFN-gamma could induce class I antigens. Similar results were obtained with the murine colon carcinoma CT-26, a tumor that constitutively expresses class I MHC antigens, further supporting the contention that class I MHC expression is not essential for the rejection response induced by IFN-gamma. The failure of SP1/IFN-gamma cells to protect against a challenge with parent SP1 cells argues that factors other than IFN-gamma production or class I MHC expression are needed to induce a protective response against weakly or nonimmunogenic tumor cells.
Esumi
N
N
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Hunt
B
B
Itaya
T
T
Frost
P
P
D000230:Adenocarcinoma / Q000209:etiology / Q000276:immunology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000096:biosynthesis; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000502:physiology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics; D008808:Mice, Inbred CBA / Q000235:genetics; D008819:Mice, Nude / Q000235:genetics; D014162:Transfection
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma