The Aberrant Activation of NLRP3 in Microsatellites Stability Colon Cancer Promotes M2 Macrophage Polarization Based on the TCGA Database and Tissue Microarray Analysis.

[BACKGROUND] Microsatellites stability (MSS) colon cancer patients exhibit a significant suppressive immune status, and the functional status of tumor NLRP3 immunosomes plays an important role in regulating the tumor immune microenvironment, but whether they are involved in the regulation of immunosuppression in MSS patients is unclear. Therefore, further exploration of the relevant molecular mechanisms is urgently needed.

[METHODS] The Cancer Genome Atlas-Colorectal Cancer (TCGA-COAD) Masked Somatic Mutation data, clinicopathological data were obtained, analyzed, and visualized using the 'maftools' in R package. Tissue microarray (TMA) used for this study includes 100 unselected, non-consecutive, primary, and sporadic CRCs treated between April 2006 and October 2010 in Tianjin Medical University General Hospital and 60 adjacent noncancerous tissues. Demographic and clinicopathological variables were collected, and the clinical value and prognostic impact of NLRP3 expression were analyzed. Tissue immunofluorescence (IF) was applied to investigate the colocalization expression of NLRP3 and ASC in tumor cells. The Vectra 3.0 Automated Quantitative Pathology Imaging System was used to obtain spectral information the NLRP3-ASC colocalization was analyzed by the Fiji Plugin "Coloc2". Cytotoxic T lymphocytes and M2 macrophages in tumor tissue were evaluated by immunohistochemistry.

[RESULTS AND CONCLUSION] In patients with MSS-CRC, aberrant activation of NLRP3 immunosome was significantly associated with lymph node metastasis of tumors. It is also closely related to the polarization of M2 macrophages in the tumor microenvironment, and further affects the infiltration of CD8+T lymphocytes, thereby creating a suppressive immune microenvironment.