激动性抗CD 40抗体治疗将肿瘤微环境中的常驻调节性T细胞转化为激活的1型效应细胞
激动性抗CD40抗体治疗将肿瘤微环境中的常驻调节性T细胞转化为激活的1型效应细胞
作者： 小柯机器人 发布时间：2026/4/3 11:52:01
本期文章：《免疫》：Online/在线发表
俄勒冈健康与科学大学Katelyn T. Byrne团队的一项最新研究提出了激动性抗CD40抗体治疗将肿瘤微环境中的常驻调节性T细胞转化为激活的1型效应细胞。该项研究成果发表在2026年4月2日出版的《免疫学》上。
研究组利用时空成像和谱系追踪方法在PDAC的小鼠模型中检测肿瘤内Treg细胞的命运，其中免疫检查点阻断（ICB）（αPD-1 + αCTLA-4）联合αCD40控制肿瘤生长。肿瘤内Foxp3 + Treg细胞数量在治疗后下降，依赖于CD40激活的树突状细胞（DCs）和白细胞介素(IL)-12和干扰素(IFN)-的诱导。这种减少与细胞改变相对应；Treg细胞获得了一种“ExTreg”表型，其特征是Foxp3表达的缺失和T辅助1 （Th1）样特征（Tbet + IFN-γ + ）的获得。αCD40促进肿瘤微环境（TME）的空间重组，而Cxcr3Treg和ExTreg细胞与表达Cxcl9的DC定位于肿瘤周围。通过对T细胞受体（TCR）信号传导的原位分析，该课题组研究人员发现在肿瘤浸润性T细胞中，Treg细胞具有最高的抗原驱动激活。将肿瘤内Treg细胞重编程为Th1样效应器，揭示了这些细胞的可塑性和抗肿瘤能力。
研究人员表示，在胰腺导管腺癌（PDAC）中，激动性抗CD40 （αCD40）降低了肿瘤内调节性T（Treg）细胞的频率，尽管Treg细胞缺乏CD40的表达。
附：英文原文
Title: Agonistic anti-CD40 antibody treatment converts resident regulatory T cells into activated type 1 effectors within the tumor microenvironment
Author: Vivien I. Maltez, Charu Arora, Kyle P. Gribbin, Breanna Caruso, Margaret E. Haerr, Rina Sor, Qiaoshi Lian, Katie E. Blise, Shamilene Sivagnanam, Rosalie C. Sears, Lisa M. Coussens, Robert H. Vonderheide, Ronald N. Germain, Katelyn T. Byrne
Issue&Volume: 2026-04-02
Abstract: In pancreatic ductal adenocarcinoma (PDAC), agonistic anti-CD40 (αCD40) reduces frequencies of intratumoral regulatory T (Treg) cells despite a lack of CD40 expression on Treg cells. Here, we leveraged spatiotemporal imaging and lineage tracing approaches to examine intratumoral Treg cell fate in a mouse model of PDAC, where immune checkpoint blockade (ICB) (αPD-1 + αCTLA-4) combined with αCD40 controls tumor growth. Intratumoral Foxp3+ Treg cell numbers collapsed upon treatment, dependent on CD40-activated dendritic cells (DCs) and induction of interleukin (IL)-12 and interferon (IFN)-. This reduction corresponded with cellular alterations; Treg cells acquired an “ExTreg” phenotype characterized by loss of Foxp3 expression and acquisition of T helper 1 (Th1)-like features (Tbet+IFN-γ+). αCD40 promoted a spatially reorganized tumor microenvironment (TME), with Cxcr3 Treg and ExTreg cells localized to the tumor periphery with Cxcl9-expressing DCs. Through in situ analyses of T cell receptor (TCR) signaling, we found that ExTreg cells had the highest antigen-driven activation among tumor-infiltrating T cells. Reprogramming of intratumoral Treg cells into Th1-like effectors reveals plasticity and an anti-tumor capacity of these cells.
DOI: 10.1016/j.immuni.2026.03.011
Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00122-6