Dualistic role of tumor‐directed antibodies on carcinoma progression

Abstract

Immunosurveillance and immunoediting of tumors comprise immune reactions that check and destroy cancer cells, and form the basis of cancer immunotherapy strategies. Paradoxically, immune reactions can also facilitate tumor progression, i.e. the immune response has a dualistic role. It is currently unclear what range of immune response defines the ends of this spectrum for a given tumor. We addressed this question using a humanized murine model in which antibodies against a human‐specific tumor antigen alters progression of tumors bearing the antigen. Tumor growth was stimulated or inhibited over a linear and narrow dose range defining an immune response curve (IRC), i.e., inverse hormesis. Tuning the relative activity of one or more immune reactants further demonstrated the dualistic role of inflammation in tumor progression. The results have implications for the etiology, prevention and treatment of human cancer. This work is supported by a Samuel and Ruth Engelberg/Cancer Research Institute fellowship and the NIH.