RT/anti-SIRPα/anti-PD-1 promoted anti-tumor efficiency in a STING-dependent way.RT-induced CD47 and PD-L1 upregulation restrained radiation-induced immune priming in CRC cells. Host STING activation is critical for TAA-specific CD8+ T cross-priming, APC mobilization and myeloid compartment activation upon RT/anti-SIRPα/anti-PD-1 therapy. Here, SIRPA is linked to colorectal carcinoma.