Role of T cells in liver metastasis.

The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.

Glutamine supplementation improves the activity and immunosuppressive action of induced regulatory T cells in vitro and in vivo.

BACKGROUND: Glutamine is crucial for the activation and efficacy of T cells, and may play a role in regulating the immune environment. This study aimed to investigate the potential role of glutamine in the activation and proliferation of induced regulatory T cells (iTregs). METHODS: CD4+CD45RA+T cells were sorted from peripheral blood mononuclear cells and cultured to analyze iTreg differentiation. Glutamine was then added to the culture system to evaluate the effects of glutamine on iTregs by determining oxidative phosphorylation (OXPHOS), apoptosis, and cytokine secretion. Additionally, a humanized murine graft-versus-host disease (GVHD) model was constructed to confirm the efficacy of glutamine-treated iTregs in vivo. RESULTS: After being cultured in vitro, glutamine significantly enhanced the levels of Foxp3, CTLA-4, CD39, CD69, IL-10, TGF-ß, and Ki67 (CTLA-4, IL-10, TGF-ß are immunosuppressive markers of iTregs) compared with that of the control iTregs (P < 0.05). Furthermore, the growth curve showed that the proliferative ability of glutamine-treated iTregs was better than that of the control iTregs (P < 0.01). Compared with the control iTregs, glutamine supplementation significantly increased oxygen consumption rates and ATP production (P < 0.05), significantly downregulated Annexin V and Caspase 3, and upregulated BCL2 (P < 0.05). However, GPNA significantly reversed the effects of glutamine (P < 0.05). Finally, a xeno-GVHD mouse model was successfully established to confirm that glutamine-treated iTregs increased the mice survival rate, delayed weight loss, and alleviated colon injury. CONCLUSION: Glutamine supplementation can improve the activity and immunosuppressive action of iTregs, and the possible mechanisms by which this occurs are related to cell proliferation, apoptosis, and OXPHOS.

Application of Laennec extrathecal blockade combined with indocyanine green fluorescence imaging in laparoscopic anatomic hepatectomy.

OBJECTIVE: To investigate the safety and application value of combining Laennec extracapsular occlusion with ICG fluorescence imaging in laparoscopic anatomic hepatectomy. METHODS: Complete laparoscopic dissection was performed outside the Laennec sheath, blocking Glisson's pedicle of the corresponding liver segment or lobe. An appropriate amount of indocyanine green (ICG) dye was intravenously injected, and the boundary line between the pre-cut liver segment and liver lobe was identified using fluorescence laparoscopy. Complete resection of the liver segment or lobe was performed based on anatomical markers. Clinical data, including operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications, were collected. RESULTS: A total of 14 cases were included in the study, including seven cases of primary liver cancer, three cases of metastatic liver cancer, three cases of intrahepatic bile duct calculi, and one case of hepatic hemangioma. All 14 patients underwent anatomic hepatectomy under fluorescent laparoscopy, with four cases involving the right liver, seven cases involving the left liver, two cases involving the right anterior lobe, and one case involving the right posterior lobe. CONCLUSION: Combining laparoscopic follow-up of the Laennec membrane with Glisson outer sheath block and intraoperative ICG fluorescence imaging provides real-time guidance for locating the resection boundaries during anatomic hepatectomy. This approach helps in controlling intraoperative bleeding, reducing operation time, and ensuring high safety. It holds significant value in clinical application.