Regulatory mucosa-associated invariant T cells controlled by ß1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression.

BACKGROUND AND AIMS: The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored. APPROACH AND RESULTS: Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3 + CXCR3 + MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3 - CXCR3 + MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by ß1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes. CONCLUSIONS: Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.

Application of RNA processing factors for predicting clinical outcomes in colon cancer.

Background: Colon cancer is the fifth most common cause of cancer-related death worldwide, and despite significant advances in related treatment, the prognosis of colon cancer patients remains poor. Objective: This study performs systematic bioinformatics analysis of prognostic-associated RNA processing factor genes in colon cancer using the Cancer Related Genome Atlas database to explore their role in colon carcinogenesis and prognosis and excavate potential therapeutic targets. Methods: Data sets of colon cancer patients were obtained from GEO and TCGA databases. Univariate cox analysis was performed on the GSE39582 training set to identify prognosis-associated RNA processing factor genes and constructed a muticox model. The predictive performance of the model was validated by Correlation curve analysis. Similar results were obtained for the test dataset. Functional analyses were performed to explore the underlying mechanisms of colon carcinogenesis and prognosis. Results: A constructed muticox model consisting of ßi and prognosis-related RNA processing factor gene expression levels (Expi) was established to evaluate the risk score of each patient. The subgroup with a higher risk score had lower overall survival (OS), higher risk factor, and mortality. We found that the risk score, age, gender, and TNM Stage were strongly associated with OS, and the 13-gene signature as an independent prognostic factor for colon cancer. The model has good accuracy in predicting patient survival and is superior to traditional pathological staging. Conclusion: This study proposes 13 RNA processing factor genes as a prognostic factor for colon cancer patients, which can independently predict the clinical outcome by risk score. The gene expression profile in this model is closely related to the immune status and prognosis of colon cancer patients. The interaction of the 13 RNA processing factor genes with the immune system during colon carcinogenesis provides new ideas for the molecular mechanisms and targeted therapies for colon cancer.

Liver Transplantation in Acute-on-Chronic Liver Failure: Excellent Outcome and Difficult Posttransplant Course.

Background: Acute-on-chronic liver failure (ACLF) patients have high mortality in a short period of time. This study aimed to compare the prognosis of transplanted ACLF patients to that of nontransplanted ACLF patients and decompensated cirrhosis recipients. Methods: Clinical data of 29 transplanted ACLF patients, 312 nontransplanted ACLF patients, and 60 transplanted decompensated cirrhosis patients were retrospectively collected. Propensity score matching (PSM) analysis was used to match patients between different groups. Results: After PSM, the 90-day and 1-year survival of transplanted ACLF patients was significantly longer than that of nontransplant controls. Although the 90-day survival and 1-year survival of ACLF recipients was similar to that of decompensated cirrhosis controls, ACLF recipients were found to have longer mechanical ventilation, longer intensive care unit (ICU) stay, longer hospital stay, higher incidence of tracheotomy, higher expense, and higher morbidity of complication than matched decompensated cirrhosis controls. The 90-day and 1-year survival of transplanted ACLF grade 2-3 patients was also significantly longer than that of nontransplanted controls. Conclusions: Liver transplantation can strongly improve the prognosis of ACLF patients. Despite having more burdens (including longer mechanical ventilation, longer ICU stay, higher incidence of tracheotomy, longer hospital stay, higher hospitalization expense, and higher complication morbidity), ACLF recipients can obtain similar short-term and long-term survival to decompensated cirrhosis recipients. For severe ACLF patients, liver transplantation can also significantly improve their short-term and long-term survival.

Pretransplant use of toripalimab for hepatocellular carcinoma resulting in fatal acute hepatic necrosis in the immediate postoperative period.

Immune checkpoint inhibitors are increasingly used in the treatment of various solid tumors, including hepatocellular carcinoma (HCC). For liver transplant recipients, the safety of using immune checkpoint inhibitors before or after transplantation remains to be further explored. Former reports were mainly about posttransplant use of immune checkpoint inhibitors resulting in allograft rejection. Here we present one HCC patient who received toripalimab (an immune checkpoint inhibitor currently in phase 3 clinical trial for HCC) therapy before undergoing liver transplantation. He finally suffered fatal acute hepatic necrosis which is likely to be related to the acute immune rejection caused by the pretransplant use of toripalimab.