LOCAL ANERGY RATHER THAN SYSTEMIC ANTITUMOR IMMUNITY TO EXPLAIN TUMOR-GROWTH IN AN ANIMAL-MODEL OF ORAL SQUAMOUS-CELL CARCINOMA

A chemically induced syngeneic hamster tumour model of human oral squa mous cell carcinoma (OSCC) was used to investigate the possible influe nce of locally transplanted growing rumours on the immune system of th e recipient. Cell activation and cell cytotoxicity assays were perform ed in vitro using the colorimetric MTT assay to measure any possible c hanges. The fast growing nature of the tumour model if grafted locally as a fragment was confirmed but not if injected as a single cell susp ension (SCS). Stimulation (Concanavalin A) of spleen cells from normal and from tumour bearing animals showed that there was a minor though statistically significant decrease in the mitogenic response of the la tter. Thus, the respective stimulatory indices (SI) were 4.06+/-1.61 a nd 2.06+/-0.87 (0.02<p>0.01). No significant difference was observed w hen spleen cells were stimulated with interleukin-2 (IL-2), although t here was a similar trend. Pre-immunisation of animals with irradiated autologous SCS three weeks prior to grafting, resulted in a significan t decrease in the tumour growth rate of subsequently grafted tumour. T hus, the mean If: SD (weight of takes in mg) for the successful takes of untreated (n=10) and treated (n=9) groups were 52.0+/-52.2 and 25.7 +/-19.4 (0.02<p>0.05) respectively. The number of cases with no tumour takes were 2 of 10 (20%) and 6 of 9 (66%) respectively. In a separate experiment groups of 5 animals were immunized with an increasing numb er of cells as irradiated SCS, the results of which demonstrated an in verse correlation between the rate of tumour growth and the number of injected tumour cells. The addition of irradiated SCS to IL-2 activate d normal spleen cells (LAK cells) in vitro led to a dose-related decre ase in the efficiency of cytotoxicity of latter when tested against an xenogeneic super-sensitive surrogate tumour target cell line (Fen cel ls). Thus, the percent killing by IL-2-activated normal spleen cells w as 56.4%. The corresponding mean values for IL-2 activated normal sple en cells in the presence of tumour SCS at 25/1 and 50/1 ratios were 35 .9% (p<0.05) and 11.9% (p<0.001) respectively. Ln an attempt to establ ish the presence of T suppressor cells, spleen cells from tumour beari ng animals were injected concomitantly with SCS into 5 recipients. Aft er four weeks no tumour growth had occurred. In conclusion we demonstr ated that the presence of injected or grafted tumour had only a minor effect on systemic immune function but induced a strong local anergic effect. This local anergic effect was demonstrable as blocking of LAK activity and thus perhaps allowed suppression of the functional activi ties of incoming immunocompetent cells.