From association to intervention: Rethinking CD24’s causal role in hepatocellular carcinogenesis

Table 2 Comparative analysis of “don’t eat me” signals in hepatocellular carcinoma immunotherapy

Checkpoint	Ligand/receptor	Expression pattern	Clinical development	Advantages	Limitations
CD24	Siglec-10	CSCs, activated immune cells, hepatocytes	Preclinical (SWA11 mAb, CAR-T)	Low normal tissue expression, dual innate/adaptive function	Heterogeneous expression, shedding-mediated decoy effects
CD47	SIRPα	Ubiquitous (high on RBCs)	Phase I/II (Hu5F9-G4, magrolimab)	Well-established biology, broad tumor coverage	On-target anemia, dosing limitations
PD-L1	PD-1	Inducible on tumor and immune cells	Approved (atezolizumab, durvalumab)	Proven efficacy, established biomarkers	Primary resistance, immune-related adverse events
MHC-I	LILRB1/2	Variable across HCC subtypes	Early preclinical	Alternative escape mechanism	Complex regulation, technical challenges

CAR-T: Chimeric antigen receptor T cell; CSCs: Cancer stem cells; HCC: Hepatocellular carcinoma; Hu5F9-G4: Humanized anti-CD47 monoclonal antibody (5F9-G4; magrolimab); LILRB1/2: Leukocyte immunoglobulin-like receptor subfamily B member 1/2; MHC-I: Major histocompatibility complex class I; PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand 1; RBCs: Red blood cells; Siglec-10: Sialic acid-binding Ig-like lectin 10; SIRPα: Signal regulatory protein alpha; SWA11: Anti-CD24 monoclonal antibody (clone SWA11).