Regorafenib enhances anti-PDCD1/PD-1 therapeutic efficacy in colorectal cancer by promoting SQSTM1/p62-mediated CD274/PD-L1 degradation

: 3-MA: 3-methyladenine; ATG5: autophagy related 5; ATG7: autophagy related 7; CD274/PD-L1: CD274 molecule; CHX: cycloheximide; co-IP: co-immunoprecipitation; CQ: chloroquine; CRC: colorectal cancer; CTLs: cytotoxic T cells; ECD: extracellular domain; GZMB: granzyme B; ICD: intracellular domain; IF: immunofluorescence; IFNG/IFN-γ: interferon gamma; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; mCRC: metastatic colorectal cancer; mIF: multiplex immunofluorescence; MSS: microsatellite stable; ORRs: objective response rates; PDCD1/PD-1: programmed cell death 1; PDCD1i: PDCD1 inhibitor; pMMR: mismatch repair-proficient; PROTACs: proteolysis-targeting chimeras; SPR: surface plasmon resonance; SQSTM1/p62: sequestosome 1; TKI: multikinase inhibitor; TME: tumor microenvironment; WB: western blot; WT: wild-type.