国家癌症中心马飞等研究人员合作揭示三阴性乳腺癌中化疗与PD-L1阻断组合的不同细胞机制。2025年2月6日，《癌细胞》杂志在线发表了这一最新研究成果。

据研究人员介绍，将免疫检查点抑制（ICB）与化疗结合用于治疗三阴性乳腺癌（TNBC）显示出希望，尽管其机制仍未完全理解。

研究人员整合了已发布和新的单细胞RNA测序（scRNA-seq）数据，以揭示接受紫杉醇（PTX）、纳米紫杉醇（Nab-PTX）及其与抗PD-L1抗体阿替利珠单抗（ATZ）组合治疗的TNBC患者的肿瘤免疫微环境（TIME）。与ATZ加PTX相比，ATZ加Nab-PTX重塑了TCF7⁺干样效应记忆CD8⁺ T细胞（Tsem）和CD4⁺ T滤泡辅助（Tfh）细胞。与PTX不同，纳米紫杉醇还重塑了髓系区室，扩展了肥大细胞和促炎巨噬细胞。

研究人员在人体TNBC和小鼠模型中的分析强调了肥大细胞在协调抗肿瘤免疫反应中的关键作用，可能是通过促进T细胞和B细胞的招募和激活。体内实验表明，激活肥大细胞与PD-L1阻断联合使用能够减缓TNBC进展，提示肥大细胞作为增强ICB治疗效果的有前景的辅助因子。

附：英文原文

Title: Distinct cellular mechanisms underlie chemotherapies and PD-L1 blockade combinations in triple-negative breast cancer

Author: Yuanyuan Zhang, Hongyan Chen, Hongnan Mo, Ning Zhao, Xiaoying Sun, Baolin Liu, Ranran Gao, Binghe Xu, Zemin Zhang, Zhihua Liu, Fei Ma

Issue&Volume: 2025-02-06

Abstract: Combining immune checkpoint blockade (ICB) with chemotherapy shows promise for treating triple-negative breast cancer (TNBC), though the mechanisms remain incompletely understood. Here, we integrate published and new single-cell RNA sequencing (scRNA-seq) data to investigate the tumor immune microenvironment (TIME) in TNBC patients treated with paclitaxel (PTX), nab-paclitaxel (Nab-PTX), and their combinations with the anti-PD-L1 antibody atezolizumab (ATZ). Compared to ATZ plus PTX, ATZ plus Nab-PTX rewires TCF7+ stem-like effector memory CD8+ T cells (Tsem) and CD4+ T follicular helper (Tfh) cells. Nab-paclitaxel, unlike PTX, also reshapes the myeloid compartment, expanding mast cells and pro-inflammatory macrophages. Our analyses in human TNBC and murine models underscore the crucial role of mast cells in orchestrating anti-tumor immune responses, likely by promoting the recruitment and activation of T and B cells. In vivo experiments demonstrate that activating mast cells alongside PD-L1 blockade attenuates TNBC progression, suggesting mast cells as a promising adjunct for enhancing ICB therapy efficacy.

DOI: 10.1016/j.ccell.2025.01.007

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00025-X