Fig. 1.

The local HCC immune landscape can be divided into immune effectors and immune regulators.

The local HCC immune landscape can be divided into immune effectors that can respond to HCC by producing a variety of mediators with anti-tumour potential (e.g. tissue-resident T cells, left top and middle panel) and immune regulators that suppress and/or exclude these immune effectors through membrane-bound checkpoint inhibitors (e.g. PD-L1) and soluble mediators (e.g. TGF-b, right top and middle panel). The balance of these opposing activities results in tumour control or growth, respectively. The goal of immunotherapies is to overcome immune exclusion/cold tumours (right bottom panel) and block negative immune regulators to allow influx and function of immune effectors for tumour shrinkage (bottom left panel). Key cellular subsets, soluble mediators and structural elements contributing to these processes are shown. Immune hot tumour – red tumour, immune cold/excluded tumour – blue (bottom panels). CAF, cancer-associated fibroblast; DC, dendritic cell; gMDSC, granulocytic myeloid derived suppressor cell; IL-, interleukin; IDO, idoleamine 2,3 dioxygenase; IFN-y, interferon γ; MAIT cell, mucosal-associated invariant T cell; mMDSC, monocytic myeloid derived suppressor cell; NK cell, natural killer cell; TAM, tumour associated macrophage; TGFβ, transforming growth factor-β; TLS, tertiary lymphoid structure; TNF-α, tumour necrosis factor-α; Treg, regulatory T cell; TRM, tissue resident memory; VEGF, vascular endothelial growth factor.