Hydrocortisone Affects Tumor Growth by Eliminating Precursors of Suppressor Cells

Abstract

Abstract Suppressor lymphocytes responsible for the suppression of anti-tumor immune response were previously demonstrated in spleens of C57BL mice carrying the syngeneic Lewis lung carcinoma (3LL). Based upon earlier observations on the inactivating effect of hydrocortisone (HC) on precursors of suppressor lymphocytes, we have now studied the effect of the steroid on the anti-tumor cellular immune response and on tumor development in 3LL-bearing mice. Mice were given a single injection of HC before, together with, or after the inoculation of 3LL tumor cells. Tumor development and mouse mortality were delayed when HC was administered after tumor inoculation. The highest delay was observed when the steroid was injected to the mice 3 to 5 days after the tumor cells. HC-resistant spleen cells (15 to 30% of the total number of cells) obtained from such tumor-bearing mice (TBM) 2 or 3 days after HC treatment enhanced tumor development significantly more than cells from untreated TBM, when transferred together with tumor cells into syngeneic recipients. However, this enhancing activity rapidly disappeared upon spleen regeneration. Spleen cells obtained 7 to 14 days after HC injection manifested a protective activity against tumor growth. These results suggest that HC affects the balance between lymphocyte subpopulations which participate in either the rejection or the enhancement of the tumor. HC-resistant spleen cells recovered from the spleens of TBM shortly after HC treatment seem to be enriched for preformed mature suppressor cells, but are deficient for their precursors. This deficiency, which is transient due to thymus and spleen regeneration, is later on expressed in an increased cytotoxic response against the tumor.