Core Viewpoint - The study highlights the enhanced formation of tertiary lymphoid structures (TLS) after FOLFOX-HAIC therapy, which shapes the anti-tumor microenvironment in hepatocellular carcinoma (HCC) [4][10]. Group 1: Research Findings - HCC is a common malignant tumor globally and the third leading cause of cancer-related deaths, with advanced HCC having poor prognosis and limited treatment options [6]. - The FOLFOX-HAIC treatment significantly improves survival rates in HCC patients, with disease remission rates ranging from 25% to 46% [6]. - The study demonstrates that FOLFOX-HAIC therapy significantly promotes the formation of TLS in HCC tissues, correlating with improved treatment outcomes and prolonged progression-free survival [6][8]. Group 2: Mechanisms of Action - HAIC induces central memory T cell-like CD4+ T cells expressing lymphotoxin-β (LTβ), which activate MMP2+ fibroblasts and FOLR2+ CCL4+ macrophages through the LTβ-LTβR signaling axis, driving TLS formation [7]. - The CXCL12-CXCR4 signaling axis plays a crucial mediating role in recruiting these cells to tumors treated with HAIC, enhancing TLS formation and anti-tumor immune response [7][8]. Group 3: Clinical Implications - The presence of TLS within tumors can predict better efficacy and prognosis for HCC patients undergoing HAIC [8]. - The collaboration between TCM-like CD4+ T cells, fibroblasts, and macrophages is essential for inducing TLS formation [8]. - The findings underscore the critical role of tumor-infiltrating lymphocytes in HAIC-induced anti-tumor immunity and their potential as reliable prognostic biomarkers, providing therapeutic targets for optimizing clinical outcomes in HCC patients [10].

Core Viewpoint - The research indicates that dietary galactose can reprogram hepatocytes to produce insulin-like growth factor binding protein-1 (IGFBP-1), which prevents T cell exhaustion and stimulates antitumor immune responses [2][3][5]. Group 1: Research Findings - High galactose diets promote hepatocytes to produce IGFBP-1, inhibiting T cell exhaustion dependent on insulin-like growth factor-1 (IGF-1) signaling [5]. - The absence of IGF-1 receptor (IGF-1R) in T cells enhances antitumor CD8+ T cell responses and prevents T cell exhaustion, demonstrating a phenotype associated with high galactose feeding [5]. - Galactose in the circulatory system reprograms hepatocyte metabolism, inhibiting mTORC1 activity and inducing IGFBP-1 production to enhance CD8+ T cell function [5]. Group 2: Clinical Observations - In cancer patients, those with higher plasma levels of IGFBP-1 exhibited reduced T cell exhaustion and enhanced T cell responses in tumor tissues [5]. - These findings suggest that dietary galactose can specifically stimulate robust antitumor CD8+ T cell responses, providing new insights for developing more effective cancer immunotherapies [5].