柳叶刀子刊：杜峻峰/吴斌合作揭示直肠癌抗肿瘤体液免疫的核心枢纽——成熟三级淋巴结构

Core Viewpoint - The study highlights the critical role of mature tertiary lymphoid structures (mTLS) in mediating B cell-driven antitumor immunity in locally advanced rectal cancer (LARC) and discusses the detrimental effects of neoadjuvant therapy (neoTx) on mTLS [4][8]. Group 1: Research Findings - The research team conducted a multi-omics analysis on 161 LARC patient samples from two clinical centers, identifying mTLS and immature TLS (iTLS) through various techniques [6]. - mTLS tumors exhibited significant enrichment of B cells and plasma cells compared to iTLS, with bulk RNA sequencing revealing upregulation of plasma cell and follicular B cell-related gene signatures [6]. - Single-cell RNA sequencing indicated that plasma cells in mTLS not only had a higher proportion but also demonstrated greater clonal diversity and stronger immunoglobulin production capabilities, particularly for IgG and IgA [6]. Group 2: Clinical Implications - The presence of mTLS and high expression of plasma cell marker CD138 were significantly associated with longer overall survival (OS) in patients, suggesting that mTLS and B cell immunity are favorable prognostic markers in rectal cancer [7]. - Analysis of 125 patients undergoing neoTx revealed that while T cell infiltration increased, the proportion of mTLS significantly decreased, indicating that neoTx primarily activates T cell-mediated immunity at the expense of mTLS structures [8]. - In patients who did not respond to neoTx, B cell-related gene signatures and CD20⁺ B cell infiltration were significantly higher despite no increase in mTLS, suggesting a compensatory B cell immune response independent of mTLS, which may relate to treatment resistance [8]. Group 3: Future Directions - The findings underscore the importance of mTLS in the tumor microenvironment of rectal cancer and the complex remodeling effects of standard neoTx on immune responses [8]. - These insights provide a theoretical basis and potential biomarkers for developing new treatment strategies aimed at preserving or leveraging B cell immunity, particularly in conjunction with neoTx [8].