Treating liver cancer through arginine depletion

The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma

“…In an analysis of fecal samples from patients receiving ICIs, taxa richness and gene counts were greater in responders [ 102 ]. Microbial dissimilarity was also detected in the fecal microbiota between responders and nonresponders among patients with unresectable HCC [ 7 ]. According to human research on melanoma, patients who were responsive to ICIs had a greater diversity of fecal microbiota and a greater abundance of Ruminococcaceae.…”

“…In one trial, three out of ten (30%) metastatic melanoma patients achieved clinical responses and tumor regression. One achieved a complete response and two achieved partial responses after receiving FMT from responders and reinitiating anti-PD-1 therapy [ 7 , 101 ]. In addition, probiotics can maintain the gut microbial balance, sustain the integrity of the intestinal barrier, and prevent leakage and migration of microbial metabolites into circulation.…”

“…The majority of patients (approximately 65–70%) are diagnosed with HCC at intermediate or advanced stages, thus missing the opportunity to receive radical resection or liver transplantation [ 7 ]. Due to the critical role of the immune system, immunotherapy has proven effective in various clinical trials for restoring innate and adaptive immunity and reversing the immunosuppressive tumor microenvironment (TME).…”

“…Due to single-agent ICIs’ poor ability to increase overall survival (OS), combined strategies, such as the combination of atezolizumab and bevacizumab, have been proposed and evaluated in clinical trials [ 9 ]. Combining immunotherapy with other strategies may constitute a useful method for treating HCC, as complex mechanisms and efficacy-determining factors underlie ICI resistance, including metabolic reprogramming of the HCC TME has garnered increasing attention [ 7 , 10 , 11 ].…”