COLON ADENOCARCINOMA CELLS INHIBIT ANTI-CD3-ACTIVATED KILLER-CELL INDUCTION

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells ha s shown some promise in the treatment of certain cancers that are unre sponsive to conventional treatment approaches. However, colon adenocar cinomas tend to respond poorly to LAK therapy, possibly as a result of tumor-induced immunosuppression. Recently, in vivo administration of anti-CD3 antibody has been shown to induce mouse T lymphocytes to medi ate major-histocompatibility-complex(MHC)-unrestricted tumoricidal act ivity which is distinct from natural-killer-cell-derived LAK activity. It has therefore been suggested that anti-CD3 therapy may find applic ation in tumor immunotherapy in humans. However, the effectiveness of anti-CD3-activated killer cell induction within the environment found in the vicinity of colon adenocarcinoma cells has not been evaluated. The present report demonstrates that colon cancer cells of human (HT-2 9) and mouse (MCA-38) origin markedly inhibit the generation of activa ted killer cells in murine spleen cell cultures. DNA synthesis and int erleukin-2 production by spleen cells following stimulation with anti- CD3 antibody are also profoundly depressed in the presence of MCA-38 a nd HT-29 adenocarcinoma cells. MCA-38- and HT-29-mediated inhibition o f activated killer cell development is exerted through the production of a tumor-associated soluble factor that is distinct from transformin g growth factor P or prostaglandins. Local immunosuppression associate d with sites of tumor growth may therefore represent a major obstacle to successful anti-CD3 immunotherapy of certain colon adenocarcinomas.