Enhancing immune response in advanced HCC with PVTT: rivaroxaban as a core adjuvant in combined therapy

Despite the establishment of combined local and systemic therapy as the standard approach for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), its efficacy remains constrained by two primary challenges: the immunosuppressive tumor microenvironment (TME) and treatment resistance. Recent research shows that factor Xa (FXa) boosts programmed death-ligand 1 (PD-L1) expression in tumor cells via the proteinase-activated receptor-2 (PAR-2) and signal transducer and activator of transcription 2 (STAT2) pathways, aiding immune evasion. Rivaroxaban, an FXa inhibitor, prevents portal vein thrombosis and disrupts the FXa/PAR-2/PD-L1 axis, restoring T cell function. Based on this mechanism, we propose that incorporating rivaroxaban as a core adjuvant into a long-term, 'local-targeted-immune' multimodal strategy can spatiotemporally reprogram the TME in advanced HCC with PVTT. This approach has the potential to effectively overcome treatment resistance and achieve sustained disease control. The hypothesis is readily testable in clinical trials, and if substantiated, it could establish a new treatment paradigm aimed at improving the prognosis for this high-risk patient population. Furthermore, it would provide a robust theoretical rationale and practical guidance for advancing the treatment of advanced HCC with PVTT.