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. 2023 Jun 22;13:1200646. doi: 10.3389/fonc.2023.1200646

Figure 1.

Figure 1

Tumor cell intrinsic and extrinsic mechanisms of resistance to immunotherapies. Schematic cartoon of some mechanisms of resistance to immunotherapies highlighting 11 tumor cell-dependent relevant mechanisms (left), and 10 mechanisms dependent on the microenvironment surrounding the tumor (right). Among the tumor extrinsic mechanisms, distinct immune cell types and stroma/endothelial cells are depicted which play a contributing role - or are affected by the overall TME immunosuppression. PD-L1 - programmed death-ligand 1; MHC-I - major histocompatibility complex class I; TAP - Transporter associated with antigen processing protein complex; ER, endoplasmic reticulum; CALR - calreticulin; JAK1 - Janus kinase 1; JAK2 - Janus kinase 2; B2M - beta-2 microglobulin; IFN - interferon; PTEN- phosphatase and tensin homolog protein; PI3K/AKT - phosphoinositide 3-kinase/Protein kinase B; HLA-G - human leukocyte antigen G; ILT2- Human inhibitory receptors Ig-like transcript 2; ILT4 - Human inhibitory receptors Ig-like transcript 4; CCL5 - C-X-C motif chemokine ligand 5; CCL7 - C-X-C motif chemokine ligand 7; CXCL8 - C-X-C motif chemokine ligand 8; CCL4 - C-C motif chemokine ligand 2; VISTA - V-domain Ig suppressor of T cell activation; LAG3 - lymphocyte-activation gene 3, TIM3 - T cell immunoglobulin and mucin domain-containing 3; TIGIT - T cell immunoreceptor with Ig and ITIM domains; CTLA4 – cytotoxic T-lymphocyte associated protein 4; TGF-beta - transforming growth factor beta; Tregs – regulatory T cells; IL-10 – interleukin10; IL-35 – interleukin 35; CXCL12 - C-X-C motif chemokine ligand 12; CCR4 - C-C chemokine receptor 4; PI3K gamma - phosphoinositide 3-kinase gamma; MDSC, myeloid-derived suppressor cells; IDO1 - indoleamine 2,3-dioxygenase enzyme, PGE2 - prostaglandin E2; CAF – cancer associated fibroblasts; NK – natural killer cells; N2 – neutrophil type 2; M2 macrophage – macrophages type 2; Breg – B regulatory cells; Th17 – T helper 17 cells; Th2 – T helper 2 cells.