Single-cell sequencing, SIRPα, CD209, Antigen-presenting cells, Radiation therapy, Colorectal cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

Abstract Objective 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). Methods 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. Results 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. Conclusion 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.