Majority of chemotherapeutic agents can elicit antitumor immunity and modulate the composition, density, function, and distribution of tumor infiltrating lymphocytes, to influence differential therapeutic responses and prognosis in cancer patients. The clinical success of these agents, particularly platinum based agents like oxaliplatin, not only depends on their cytotoxic activity but also by the enhancement of pre-existing immunity primarily through induction of immunogenic cell death. However, resistance for the induction of immunogenic cell death either intrinsic or acquired is a major hurdle for most of these drugs. In order to enhance immunogenic cell death by these agents, it has become clear that blockade of adenosine production or its signaling need to be specifically targeted as they represent highly resistant mechanisms. Given the prominent role of adenosine mediated immunosuppression and resistance to immunogenic cell death induction in tumor micro environment, combination strategies that involve immunogenic cell death induction and adenosine signaling blockade are further warranted. The purpose of the present study is to investigate the combination therapy of oxaliplatin and caffeine against carcinogen and cell-line induced tumor models in mice. Study results demonstrated significant tumor growth inhibition by the oxaliplatin and caffeine combination therapy against both the tumor models. Additionally, significant T-cell infiltration and enhanced immunogenic cell death induction evidenced by increased intra-tumoral calreticulin and HMGB1 levels, was observed in B16F10 melanoma mice

Immunogenic cell death; Adenosine A2A receptor; Anti-tumor immune response; Cancer immunotherapy; Chemotherapy