NLRP6 deficiency suppresses colorectal cancer liver metastasis growth by modulating M-MDSC-induced immunosuppressive microenvironment

Colorectal cancer liver metastasis (CRLM) a profound influence on the prognosis of patients with colorectal cancer (CRC), prompting a comprehensive inquiry into its underlying mechanisms. Amidst the multifaceted tumor microenvironment, myeloid-derived suppressor cells (MDSCs) have emerged as pivotal orchestrators of immune modulation. However, their specific contributions to the CRLM have not been explored. The role of NLRP6, a member of the NOD-like receptor family, is of interest. Employing a liver metastasis model, our investigation revealed a heightened accumulation of monocytic MDSCs (M-MDSCs) within metastatic sites, culminating in an immunosuppressive milieu characterized by depleted CD8+ T cell populations. Remarkably, the absence of NLRP6 disrupts this intricate immunosuppressive network, highlighting its nuanced role in sculpting the trajectory of CRLM. This study elucidates the interplay between NLRP6 and MDSCs, potentially guiding novel therapeutic strategies to recalibrate the immune microenvironment in CRLM and enhance patient outcomes. [Display omitted] •NLRP6 deficiency suppresses hepatic metastatic growth in colorectal cancer.•NLRP6 contributes to the formation of an immunosuppressive microenvironment in colorectal cancer liver metastasis.•NLRP6 is involved in the interaction between tumor cells and M-MDSCs.