Schwannoma cells induce a tumor-cell-specific cytotoxic-T-cell response upon transplantation into syngeneic rats but escape elimination through the secretion of immunosuppressive factors.
Tumor cells often express antigens that can be recognized by the immune system. Despite induction of an immune response, the tumor cells escape their elimination. We have studied the mechanisms and factors which mediate these events in a syngeneic tumor model. NV2Cd rat schwannoma cells were transplanted into BDIX rats. After injection of 10(7) to 2 x 10(7) cells, tumors grew very slowly for 10 to 12 days. After that time, rapid growth was observed. The tumors consisted of compact areas of spindle-shaped cells with small cysts, many blood vessels and central necrotic areas. During tumor growth, the number of spleen cells and T lymphocytes increased, and cytotoxic T cells with specificity for the NV2Cd tumor cells were detected. The strong specific cellular immune response did not prevent the increase in tumor volume. We studied the biological activity of the fluid present in the cysts of the tumor. At a concentration of 1 ng to 10 microg protein per ml, the cyst fluid inhibited the proliferation of splenic T lymphocytes and B lymphocytes and of lymphoma cells, but enhanced the proliferation of NV2Cd tumor cells. The cyst fluids contain the immunosuppressive transforming growth factors (TGF)-beta1, -beta2 and -beta3, also the vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Antibodies directed against TGF-beta relieved the suppression of T-cell growth by cyst fluid, but did not influence the proliferation of NV2Cd cells. The growth-modulating factors present in the tumor cyst fluid were also detected in conditioned medium from NV2Cd cells cultured in vitro. Our data suggest that tumors can escape the cellular immune response by the production of factors that inhibit lymphocytes. They also enhance their own growth environment by secreted factors.
Altenschmidt
U
U
Institute for Experimental Cancer Research, Tumor Biology Center, Freiburg, Germany.
Kahl
R
R
Klundt
E
E
Stöcklin
E
E
Mihatsch
M
M
Weindel
K
K
Groner
B
B
D000818:Animals; D016516:CD4-CD8 Ratio; D016228:Endothelial Growth Factors / Q000276:immunology; D004815:Epidermal Growth Factor / Q000378:metabolism; D007108:Immune Tolerance; D007111:Immunity, Cellular; D008222:Lymphokines / Q000276:immunology; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000276:immunology; D009442:Neurilemmoma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004815:Epidermal Growth Factor