CCL2 Blockade Augments Cancer Immunotherapy

摘要: Altering the immunosuppressive microenvironment that exists within a tumor will likely be necessary for cancer vaccines to trigger an effective antitumor response. Monocyte chemoattractant proteins (such as CCL2) are produced by many tumors and have both direct indirect immunoinhibitory effects. We hypothesized CCL2 blockade would reduce immunosuppression augment vaccine immunotherapy. Anti-murine CCL2/CCL12 monoclonal antibodies were administered in three immunotherapy models: one aimed at human papillomavirus E7 antigen expressed non-small cell lung (NSCLC) line, targeted mesothelin mesothelioma using adenovirus-expressing IFN-alpha treat nonimmunogenic NSCLC line. evaluated effect of combination treatment on growth assessed mechanism these changes evaluating cytotoxic T cells, microenvironment. Administration anti-CCL2/CCL12 along with markedly augmented efficacy enhanced reduction volume cures approximately half tumors. The combined generated more total intratumoral CD8+ cells activated antigen-specific, measured tetramer evaluation. Another important potential was regulatory cells. seems key proximal cytokine mediating Its augments T-cell immune response elicited via multifactorial mechanisms. These observations suggest combining neutralization should considered future trials.