Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma.

Glutamine metabolism is critical both for the proliferation of cancer cells and the activation of CD8T cells to kill cancer cells. We aim to explore the relationship between the glutamine metabolism of CD8T cells and cancer cells and tumor immunity in the tumor microenvironment. In a TCGA cohort, we found that patients with high scores of glutamine-metabolism-related genes showed poor prognoses, and that a high score of glutamine-metabolism-related genes was an independent risk factor for HCC patients. In single-cell RNA-seq data, we found that, in some patients, the glutamine metabolism gene scores of tumor cells were significantly higher than those of CD8T cells, while decreased ratios of CD8-Tef-GZMA and suppressed tumor-killing activity of CD8-Tef-APOC2 were observed. A further genetic dynamics pseudotime analysis suggested that immune remodeling of these two subpopulations was accompanied by metabolic reprogramming. CD8-Tef-APOC2 in the dominant group tended to metabolize exogenous lipids, while the metabolic program of CD8-Tef-GZMA in the nondominant group was characterized by amino acid and endogenous lipid synthesis. In addition, we found that the glutamine metabolism inhibitor JHU083 promoted the proliferation of CD8T cells and improved the efficacy of PD-1 blockers. We proposed a new tool to quantify the glutamine partitioning between tumor cells and CD8T cells, through which the unique immune microenvironment could be identified at the transcriptome level. Furthermore, the simultaneous destruction of the glutamine metabolism in tumor cells and CD8T cells facilitated the enrichment of tumor-infiltrating CD8T cells and enhanced the efficacy of immunotherapy.

Immune checkpoint inhibitor-induced colitis complicated with inflammatory intestinal obstruction: a case report and literature review.

Background: The combination therapy using anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) has an excellent safety profile and manageable toxicity. However, ICI therapy may lead to a variety of autoimmune events, known as immune-related adverse events (irAEs), which some secondary complications may occur, such as immune-mediated colitis (IMC) and secondary inflammatory intestinal obstruction. It could impact clinical assessments and treatment decisions. Although there are few reports about secondary inflammatory intestinal obstruction related IMC. Case Description: We report an adult patient who suffered from primary liver cancer, who accepted ICIs (sintilimab) combined with vascular endothelial growth factor (VEGF) inhibitor (bevacizumab). He suffered worsening diarrhea about 5 days following immunotherapy. Computed tomography (CT) revealed the thickening intestinal wall of colon and rectum and massive cerebral gas in the proximal colon cavity. He was hospitalized with a diagnosis of IMC and inflammatory intestinal obstruction. Finally, he underwent the therapeutic option using combined glucocorticoid and somatostatin. His symptoms eased within 3 weeks and he was discharged from the hospital. Conclusions: IMC with diarrhea as the main manifestation requires early diagnosis and timely treatment. If the condition progresses, inflammatory intestinal obstruction may occur and this is a life-threatening situation. It is effective to accept early glucocorticoid and somatostatin while casual surgery may aggravate intestinal inflammation and injury, even death.

Successful application of indocyanine green fluorescent imaging for the non-invasive detection of postoperative bile leakage.

There is a lack of a simple and reliable method for the diagnosis of postoperative bile leakage. ICG is a water-soluble fluorescent contrast agent. After intravenous injection of ICG, ICG is eventually excreted only through the biliary tract system into the intestines. It is highly sensitive, stable and nonradioactive, and these characteristics provide a theoretical basis for using ICG to diagnose postoperative bile leakage. Two patients with postoperative bile leakage were successfully identified using indocyanine green fluorescent imaging for the first time, suggesting its potential to be a convenient and reliable method for the diagnosis of postoperative bile leakage.

Successful application of ICG fluorescence imaging technology in rectal neuroendocrine tumor liver metastasis.

We report the use of indocyanine green fluorescence imaging technology to assist the resection of rectal neuroendocrine tumors with liver metastases. The liver metastases of rectal neuroendocrine tumors show strong fluorescent signals, the tumor borders are clear, and there is no fluorescence at the resection margin, indicating that the tumor has been completely removed. Postoperative pathology also confirmed that the tumor margin was negative. ICG fluorescence imaging has great potential in assisting the resection of liver metastases of neuroendocrine tumors, and at the same time is able to assist in judging the removal of the tumor.