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. 2023 Feb 7;12(4):530. doi: 10.3390/cells12040530

Figure 1.

Figure 1

The interaction between tumor cells and immune cells. Tumor cells are detected by adaptive (comprising of B and T cells) and innate immune system (mainly natural killer (NK) cells). Effector CD4+ and cytotoxic CD8+ T cells are capable of recognizing peptide antigens presented on MHC class II or MHC class I, respectively. (A) Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns (DAMPs) from dying cells. Such molecular patterns, whether expressed on the surface of cells or released outside of the cell, can promote tumor antigen presentation and boost adaptive immunity. Calreticulin (CRT) expressed on cancer cells interacts with the CD91 receptor on dendritic cells (DCs) and high-mobility group protein 1 (HMGB1)—a ligand for the toll-like receptor (TLR-4) receptor on DCs is released by cancer cells. Additionally, ATP released from cancer cells interacts with the P2X purinoceptor 7 (P2RX7) on DSc. (B) DCs are required for cytotoxic CD8+ T cell priming. In this process, DCs uptake antigens from tumor cells undergoing apoptosis and with the support of CD4+ helper cells present them to CD8+ T cells. Moreover, DCs can secrete tumor necrosis factor α (TNF-α,) and interleukins (IL-6, IL-8, and IL-12) that help to trigger the anticancer immune response. (C) Activated CD8+ T cells can kill cancer cells through the release of granzyme A/B (GZMA/B), perforins (PFN), or interferon gamma (INFγ) and TNFα that (D) induce cell death through the activation of the extrinsic apoptosis pathway. The extrinsic pathway is triggered with the binding of certain ligands to the TNFα receptor super family. This leads to the oligomerization of the receptor and activation of procaspase-8 through the recruitment of adaptor proteins and the formation of a death-inducing signaling complex (DISC). (E) Cancer cells reshape the tumor immune microenvironment into an immunosuppressive surrounding that is rich in regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), group 2 innate lymphoid cells (ILC2s), and tumor-associated macrophages (M2) that release immunosuppressive interleukins (IL-4, IL-10, IL-13, and IL-35) or transforming growth factor β (TGF-β) and up-regulate receptors (such as programmed cell death 1 ligand 1 (PD-L1)) that “hide” tumor cells from the immune recognition (not shown here). This topic has been extensively reviewed in [15,16,17] and will not be discussed in detail here. Casp—caspase; FADD—FAS-associated death domain protein; TCR—T-cell receptor. Created with BioRender.com accessed on 1 February 2023.