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. 2022 Sep 2;12:958720. doi: 10.3389/fonc.2022.958720

Figure 1.

Figure 1

Key mechanisms of immune checkpoint inhibitor resistance in hepatocellular carcinoma. (1) Inadequate, absence or alterations in the presentation or processing of tumor neoantigens; (2) alterations in oncogenic pathways, such as phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT),  Wnt/β-Catenin, and transforming growth factor beta (TGF-β) signaling pathways; (3 and 4) polarization toward an immunosuppressive microenvironment by reducing pro-inflammatory mediators and increasing anti-inflammatory mediators; (5) other novel immune checkpoint molecules, such as T-cell immunoglobulin and ITIM domain (TIGIT), lymphocyte activation gene-3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), B7 homolog 3 protein (B7-H3), B and T lymphocyte attenuator (BTLA), V-domain immunoglobulin suppressor of T cell activation (VISTA), and inducible T-cell costimulatory (ICOS).