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Background: Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. Methods: A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. Results: Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI β: − 1.44 to − 0.417), estimated glomerular filtration rate (eGFR) (− 0.025 to − 0.008), triglycerides (− 0.015 to − 0.005), and fibrosis-4 levels (0.08–0.297) were associated with adiponectin levels; BMI (0.029–0.327) and triglycerides levels (0.01–0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (− 1.89 to − 0.5) and eGFR (− 0.02 to − 0.001) levels were associated with adiponectin levels, levels of BMI (0.094–0.335) and alanine transaminase (0.018–0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 μg/mL, p < 0.001). In 12-month-old HCV core transgenic mice with hepatic steatosis, triglyceride levels (0.021–0.111) were associated with adiponectin levels, and hepatic adipopnectin expression was comparable with that of control mice. Conclusions: Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides. [ABSTRACT FROM AUTHOR]

Background: Cellular states of different immune cells can affect the activity of the whole immune microenvironment. Methods: Here, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of microenvironment cell states across 463 skin cutaneous melanoma (SKCM) bulk samples through CIBERSORT-based deconvolution of gene expression profiles and revealed high heterogeneity of their distribution. Correspondence analysis on the estimated cellular fractions of melanoma bulk samples was performed to identify immune phenotypes. Based on the publicly available clinical survival and therapy data, we analyzed the relationship between immune phenotypes and clinical outcomes of melanoma. Results: By analysis of the relationships among those cell states, we further identified three distinct tumor microenvironment immune phenotypes: "immune hot/active", "immune cold-suppressive" and "immune cold-exhausted". They were characterized by markedly different patterns of cell states: most notably the CD8 T Cytotoxic state, CD8 T Mixed state, B non-regulatory state and cancer-associated fibroblasts (CAFs), depicting distinct types of antitumor immune response (or immune activity). These phenotypes had prognostic significance for progression-free survival and implications in response to immune therapy in an independent cohort of anti-PD1 treated melanoma patients. Conclusions: The proposed strategy of leveraging single-cell data to dissect the composition of microenvironment cell states in individual bulk tumors can also extend to other cancer types, and our results highlight the importance of microenvironment cell states for the understanding of tumor immunity. [ABSTRACT FROM AUTHOR]