Immune microenvironment evolution and tumor metabolism reprograming during treatment of Bevacizumab containing regimen in CLM patients

We examined how the immune microenvironment molds tumor evolution in a longitudinal dataset of colorectal cancer liver metastases. Through multiplexed analyses, the immune microenvironment exerts a strong selection pressure during treatment of CLM tumor. Increasing infiltration of T cell were associated with favorable outcomes and sensitive response to chemotherapy ± Bevacizumab. Activation of fatty acid metabolism, xenobiotic metabolism, insulin receptor signaling pathway and neutrophils infiltration were observed in progressive tumors. TCR diversity in response metastatic regions was significantly increased compared with non-responder. Bevacizumab containing regimen facilitated T cell infiltrating to the tumor microenvironment which might consequently benefit from checkpoint immunotherapy. In responding patients, mutation load from plasma were reduced from baseline, but changed slightly in tumor tissues. This integrative and comparative omics analysis provides a new paradigm for understanding the evolution and treatment resistance of colorectal cancer liver metastases, with implications for identifying ways to advance treatment regimen and monitoring treatment response of colorectal cancer liver metastases. We analyzed clinical outcomes and molecular features of longitudinal specimens prospectively collected from 15 patients with CLM >>>Submitter states that raw data are unavailable due to patient privacy concerns<<<