Target immune components to circumvent sorafenib resistance in hepatocellular carcinoma

Sorafenib, a multi-kinase inhibitor, has been approved for cancer treatment for decades, especially hepatocellular carcinoma (HCC). Although sorafenib produced substantial clinical benefits in the initial stage, a large propor-tion of cancer patients acquired drug resistance in subsequent treatment, which always disturbs clinical physi-cians. Cumulative evidence unraveled the underlying mechanism of sorafenib, but few reports focused on the role of immune subpopulations, since the immunological rationale of sorafenib resistance has not yet been defined. Here, we reviewed the immunoregulatory effects of sorafenib on the tumor microenvironment and emphasized the potential immunological mechanisms of therapeutic resistance to sorafenib. Moreover, we also summarized the clinical outcomes and ongoing trials in combination of sorafenib with immunotherapy, high-lighted the immunotherapeutic strategies to improve sorafenib efficacy, and put forward several prospective questions aimed at guiding future research in overcoming sorafenib resistance in HCC.