MGLL deficiency in tumor-associated macrophages promotes immunosuppression and colorectal peritoneal metastases in mice

To investigate the effects and mechanisms of monoacylglycerol lipase（MGLL）in tumor-associated macrophages（TAMs）for the progression of colorectal cancer peritoneal metastases（CRC-PM）.

After macrophage MGLL conditional knockout（cKO）mice was constructed, a CRC-PM model was established in these cKO mice. The effects and mechanism of MGLL deficiency on TAMs were studies with cell biological and RNA-Seq assays.

Compared with the control mice, macrophage MGLL deficiency significantly shortened the survival time of CRC-PC mice（P<0.05）, increased the weight of peritoneal tumor masses（P<0.05）, diminished the percentage of T cells in the tumor microenvironment（P<0.01）, while elevated the percentage of M2 macrophages in cKO mice（P<0.05）. And the results of RNA-seq showed that TRLs, PD-1/PDL-1, and HIF-1 signal pathways were significantly changed in MGLL deficiency macrophages.

In the process of CRC-PC, MGLL deficiency leads to macrophage activation towards an M2-type phenotype and further destroys T cell-based anti-tumor immunity capacity, and ultimately promotes the progression of CRC-PC. The mechanisms may be due to the changes in TRLs, PD-1/PDL-1, and HIF-1 signal pathways.