靶向外周5-HT 2 AR增强结直肠癌的抗肿瘤免疫
靶向外周5-HT2AR增强结直肠癌的抗肿瘤免疫
作者： 小柯机器人 发布时间：2026/8/6 13:43:25
本期文章：《细胞》：Online/在线发表
复旦大学陈剑峰课题组近日取得一项新成果。经过不懈努力，他们发现了靶向外周5-HT2AR增强结直肠癌的抗肿瘤免疫。该研究于2026年8月4日发表于国际一流学术期刊《细胞》杂志上。
该课题组研究人员发现，麦角酸二乙胺（LSD）通过靶向5-羟色胺受体5-HT 2A R，增强CD8 + T细胞介导的抗肿瘤免疫，抑制结直肠癌（CRC）的生长。为了利用这种活性，同时避免迷幻效应，该团队开发了IHCH-8110，一种选择性靶向外周5-HT 2A R的非脑渗透性5-HT 2A R激动剂。该课题组发现IHCH-8110通过激活肠胶质细胞上的5-HT 2A R抑制结直肠癌的进展，从而诱导CXCL10和白细胞介素(IL)-18的表达，促进肿瘤微环境中CD8 + T细胞的募集和效应物极化。IHCH-8110通过将免疫冷结直肠癌转化为更具免疫应答性的状态，增强了PD-1阻断的疗效。总之，他们的发现确定了肠道5-HT 2A R信号作为抗肿瘤免疫的调节因子，并支持外周5-HT 2A R激动剂作为CRC免疫治疗的治疗策略。
据介绍，癌症仍然是世界范围内发病率和死亡率的主要主题。虽然经典致幻剂已被临床用于治疗癌症相关精神疾病，但它们对肿瘤进展的影响尚不清楚。
附：英文原文
Title: Targeting peripheral 5-HT2AR enhances antitumor immunity in colorectal cancer
Author: YaTing Wen, LingJie Tang, WenWen Duan, QingFei Ren, YangYue Ni, ShiYang Chen, Jun Chen, Lei Yang, Huan Wang, Yuan Chen, YunZhe Zheng, XingChao Pan, Hui Du, MengWen Huang, An Zeng, Zhaocai Zhou, ZhiGang Zhang, HongBin Ji, GaoXiang Ge, Yi Arial Zeng, Wei Zhang, ShiHui Wang, JianJun Cheng, Sheng Wang, JianFeng Chen
Issue&Volume: 2026-08-04
Abstract: Cancer remains a leading cause of morbidity and mortality worldwide. While classical psychedelics have been used clinically to treat cancer-associated psychiatric disorders, their impact on tumor progression is unclear. Here, we show that by targeting the serotonin receptor 5-HT2AR, lysergic acid diethylamide (LSD) enhances CD8+ T cell-mediated antitumor immunity and suppresses colorectal cancer (CRC) growth. To harness this activity while avoiding psychedelic effects, we developed IHCH-8110, a non-brain-penetrant 5-HT2AR agonist that selectively targets peripheral 5-HT2AR. We show that IHCH-8110 inhibits CRC progression by activating 5-HT2AR on enteric glial cells, thereby inducing CXCL10 and interleukin (IL)-18 expression to promote CD8+ T cell recruitment and effector polarization within the tumor microenvironment. By converting immune-cold CRC into a more immunologically responsive state, IHCH-8110 enhances the efficacy of PD-1 blockade. Together, our findings identify enteric 5-HT2AR signaling as a regulator of antitumor immunity and support peripheral 5-HT2AR agonists as a therapeutic strategy for CRC immunotherapy.
DOI: 10.1016/j.cell.2026.07.028
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00826-3