Immune response triggered by a novel molecular crosstalk of major hallmarks of cancer: Angiogenesis, mismatch repair, and immune pathways.

11054 Background: The development of bevacizumab to inhibit VEGF has resulted in extended PFS, however OS has failed to show significant clinical benefit in a number of cancer types. Recent data however, has shown bevacizumab to prolong OS in a subset of patients with MMR deficient tumors in adjuvant CRC. Methods: Isolated macrophages were treated with tumor-conditioned media from MMR proficient and MMR deficient tumor cells. Furthermore tumor cells were co-cultured with human monocyte-derived macrophages for analysis of phagocytic activity. Treatment regimens in vitro attempted to mimic the clinical setting by inducing DNA damage in tumor cells, and then allowing cells to recover with or without VEGF using bevacizumab treatment for 24 hrs before co-culture or collection of tumor-conditioned media. Results: Gene expression changes in macrophages induced by tumor-conditioned media showed CCL18 to be a bevacizumab regulated gene. MMR deficient tumor cell conditioned media after DNA damage showed a 68% incre...