Li Yida, Lu Weiqing, Xia Fan, Deng Yun, Jin Xin, Xuan Yan, Wang Yaqi, Shen Lijun, Wan Juefeng, Zhang Hui, Li Yaqi, Li Xinxiang, Huang Lili, Zhang Zhen
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Radiation Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.
Cancer Immunol Immunother. 2025 Apr 10;74(5):167. doi: 10.1007/s00262-025-04025-z.
Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with a need for improved treatment strategies. Antigen-presenting cells (APCs) have emerged as important modulators of immune responses in the tumor microenvironment (TME). This study aimed to explore the role of these cells in CRC and their potential synergy with radiation therapy (RT).
Single-cell sequencing was performed before and after neoadjuvant therapy (NAT) to identify changes in myeloid cells within the tumor microenvironment, which was compared with peripheral blood of the same patients. The effect of RT with/without immunotherapy on these cells was evaluated in vivo and in vitro.
Single-cell sequencing showed that SIRPα + CD209 + cells are specialized antigen-presenting cells which are found to decrease in the TME while increasing in the peripheral blood after NAT. In vitro study confirmed their resistance to RT with further upregulated SIRPα expression and enhanced antigen presentation capability induced by RT. Moreover, these cells are involved in the superior tumor control by combination of RT and anti-SIRPα treatment.
SIRPα + CD209 + APCs play a pivotal role in CRC immune modulation and show potential for synergy with RT. These cells could be a biomarker for antigen-presenting capacity, and enhancing their APC function could potentially improve RT/PD1 effectiveness by combination with anti-SIRPα in CRC.
结直肠癌（CRC）是癌症相关死亡的主要原因，需要改进治疗策略。抗原呈递细胞（APC）已成为肿瘤微环境（TME）中免疫反应的重要调节因子。本研究旨在探讨这些细胞在结直肠癌中的作用及其与放射治疗（RT）的潜在协同作用。
在新辅助治疗（NAT）前后进行单细胞测序，以识别肿瘤微环境中髓系细胞的变化，并与同一患者的外周血进行比较。在体内和体外评估有/无免疫治疗的放疗对这些细胞的影响。
单细胞测序显示，SIRPα+CD209+细胞是特殊的抗原呈递细胞，在NAT后发现其在TME中减少而在外周血中增加。体外研究证实它们对放疗有抗性，放疗可进一步上调SIRPα表达并增强抗原呈递能力。此外，这些细胞通过放疗和抗SIRPα治疗的联合参与更好的肿瘤控制。
SIRPα+CD209+APC在结直肠癌免疫调节中起关键作用，并显示出与放疗协同的潜力。这些细胞可能是抗原呈递能力的生物标志物，通过在结直肠癌中与抗SIRPα联合增强其APC功能可能会提高放疗/PD1的疗效。
