Unraveling the Complexities of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Abstract

Immune checkpoint inhibitors (ICIs) have emerged as effective therapeutics for multiple cancers. Nevertheless, as immunotherapeutic approaches are being extensively utilized, substantial hurdles have arisen for clinicians. These include countering ICIs resistance and ensuring precise efficacy assessments of these drugs, especially in the context of hepatocellular carcinoma (HCC). This review attempts to offer a holistic overview of the latest insights into the ICIs resistance mechanisms in HCC, the molecular underpinnings, and immune response. The intent is to inspire the development of efficacious combination strategies. This review also examines the unconventional response patterns, namely pseudoprogression (PsP) and hyperprogression (HPD). The prompt and rigorous evaluation of these treatment efficacies has emerged as a crucial imperative. Multiple clinical, radiological, and biomarker tests have been advanced to meticulously assess tumor response. Despite progress, precise mechanisms of action and predictive biomarkers remain elusive. This necessitates further investigation through prospective cohort studies in the impending future.

Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?

“…In general, primary resistance mechanisms are categorized into intrinsic and extrinsic mechanisms 55,56 we will describe these in the following sections, mainly focusing on the TME, as primary resistance in HCC has recently been discussed in detail in Seminars in Liver Disease. 57…”