The indispensability of the LINC01004-SPI1 axis in SIGLEC9-mediated M2 TAM reprogramming and radioresistance was confirmed by rescue experiments where knockdown of either LINC01004 or SPI1 led to an M1 shift of TAMs and consequently alleviated the immunosuppressive TME and radioresistance in ESCC. Here, SIGLEC9 is linked to esophageal squamous cell carcinoma.