Esophageal squamous cell carcinoma is the main histological type of esophageal cancer in China, which seriously threatens the health of people. The application of immunotherapy, mainly immune checkpoint inhibitors, has greatly improved the prognosis of patients with esophageal squamous cell carcinoma, but the efficacy of treatment is still limited. Tertiary lymphoid structure (TLS) is an ectopic organized lymphoid structure that accumulates in non-lymphoid organs. Previous studies have found that TLS in esophageal squamous cell carcinoma is associated with better patient outcomes and enhanced immunotherapy efficacy. Based on current researches about TLS in esophageal squamous cell carcinoma, this paper reviews the relationship between TLS and the prognosis and immunotherapy of patients. We hope to provide reference for the precise immunotherapy of esophageal squamous cell carcinoma.
Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.
ObjectiveTo systematically summarize the dynamic changes, mechanisms of action, and potential clinical translational value of neutrophils during gastric carcinogenesis and progression, thereby providing a reference for understanding the gastric cancer immune microenvironment and exploring therapeutic interventions. MethodRecent basic and clinical studies and relevant reviews were summarized and analyzed, with a focus on the Correa cascade of gastric carcinogenesis, neutrophil functional plasticity, and targeted interventions. ResultsThe Correa cascade of gastric carcinogenesis is typically accompanied by dynamic remodeling of the inflammatory microenvironment and immune cell composition. Neutrophils exhibit characteristic functional changes across the cascade. During chronic non-atrophic gastritis, they predominantly display an inflammatory phenotype and exert dual effects involving antimicrobial defense and mucosal injury. During atrophic gastritis, intestinal metaplasia, and dysplasia, neutrophil infiltration persists, although their functional states remain unclear. At the gastric cancer stage, neutrophils evolve into highly heterogeneous tumor-associated neutrophils (TANs) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which contribute to tumor progression, immune evasion, and metastasis through multiple mechanisms involving chemokine axes, immunosuppressive molecules, extracellular matrix remodeling, and neutrophil extracellular traps (NETs). The principal neutrophil-targeted strategies include blocking neutrophil recruitment to the tumor microenvironment, modulating N1/N2 polarization, interfering with NETs formation and function, and alleviating PMN-MDSC-mediated myeloid immunosuppression. These strategies have shown potential to enhance antitumor immunity and improve the efficacy of immune checkpoint inhibitors in preclinical models of gastric cancer; however, no therapy directed solely at neutrophils has yet been approved for clinical use in gastric cancer. ConclusionThe dynamic evolution and marked functional heterogeneity of neutrophils in gastric cancer provide potential targets for combination immunotherapy; nevertheless, clinical translation demands precise subtyping of neutrophils, selective intervention, and prospective validation anchored in the Correa cascade.
Objective To summarize mechanisms and research progress of bile acid (BA) regulate the immune microenvironment of hepatocellular carcinoma (HCC) through tumor-associated macrophage (TAM). MethodsRelevant studies published in China and abroad were reviewed, focusing on altered BA metabolism in HCC, BA receptor-mediated changes in TAM function, immune-cell interactions and therapeutic investigations. ResultsAlterations in BA synthesis, conjugation and transport, disrupted microbial transformation can change the composition and tissue distribution of BAs in HCC. Different BAs have different functions such as promoting TAM immunosuppression, enhance antitumor macrophage responses. BA can also directly regulate the functions of CD8+ T cells, natural killer T cells and natural killer cells. Interventions such as targeting BA production, targeting specific BA type and its receptor signaling have reduced tumor burden or enhanced immune therapy effect. Phase Ⅱ studies of BA combined with immune checkpoint inhibitors are in progress. ConclusionsAltered BA composition regulates the HCC immune microenvironment through both TAM and effector lymphocytes, the role of BA determined by its type, receptor, target cell, and disease context. Related mechaniss and therapeutic strategies require further validation in human-derived models and prospective clinical studies.
