Hepatic metastasis (HM) and lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC) are associated with worse overall survival, largely due to the immunosuppressive microenvironment. However, the key immunosuppressive cells within this microenvironment remain inadequately defined. This study aimed to identify the cells contributing to HM and lymph node metastasis in PDAC and to investigate their regulatory mechanisms.

Single-cell RNA sequencing was used to profile the tumor microenvironment in HM, lymph node-negative, and lymph node-positive (LNP) PDAC tissues. Bioinformatic analyses revealed subtypes of immunosuppressive myeloid-derived suppressor cells (MDSCs). Immunofluorescence and flow cytometry were performed to detect the distribution and proportion of interleukin-1 receptor antagonist (IL1RA+) MDSCs. The immunosuppressive and pro-tumorigenic functions of IL1RA+ MDSCs were analyzed using enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and Transwell assays. Patient-derived xenograft mouse models were employed to validate the role of IL1RA+ MDSCs in vivo.

Polymorphonuclear-MDSCs were found to be recruited to metastatic PDAC tissues. Among these, IL1RA+ MDSCs were enriched in HM/LNP tissues and correlated with poorer prognosis. IL1RA+ MDSCs promoted M2 macrophage polarization and suppressed the activity of natural killer cells and cytotoxic T cells. Furthermore, IL1RA+ MDSCs accelerated PDAC migration and progression by upregulating epithelial–mesenchymal transition-related proteins in both in vitro and in vivo models.

IL1RA+ MDSCs represent a key immunosuppressive and pro-tumorigenic subtype in HM/LNP PDAC, providing a solid theoretical basis for prognostic prediction and the development of immunotherapeutic strategies targeting these cells in HM/LNP PDAC.

Myosteatosis is associated with poor outcomes in various liver diseases. However, standardized methods for assessing, defining, and diagnosing myosteatosis in the context of liver diseases remain unclear. Furthermore, the underlying mechanisms by which myosteatosis leads to pathophysiological progression and adverse health outcomes remain elusive. Therefore, in this review, we elaborate on the currently available measures, definitions, and diagnostic criteria of myosteatosis in the existing literature. We thoroughly clarify the recent evidence and data regarding the possible involvement of myosteatosis in the progression and deterioration of various liver diseases and resulting complications, including liver cirrhosis, chronic viral hepatitis, non-alcoholic/metabolic-associated fatty liver disease, primary sclerosing cholangitis, liver transplantation, and hepatocellular carcinoma. Additionally, it synthesizes insights from basic research on the pathogenesis of myosteatosis, which involves multifactorial mechanisms, including insulin resistance, mitochondrial dysfunction, and chronic inflammation. Finally, from an operational and pragmatic perspective, several regimens, including physical, nutritional, and pharmacological therapies, have been discussed as potential treatments for myosteatosis.