Figure 2.

Tumor Microenvironment (TME). PD-L1 tumoral cell expression and PD-1 immune cell axis plays a key role in physiological immune homeostasis and contributes to tumor cell immune evasion. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) ligation to CD28 quantitatively augments TCR-mediated signals, as well as activating independent pathways to upregulate CD28-mediated cytokine production and proliferation, raising the threshold needed for T-cell activation and arresting T-cell-cycle progression. Simultaneous recognition of a specific major histocompatibility complex (MHC)–peptide complex by the T-cell receptor (TCR) and of B7-1 (CD80) or B7-2 (CD86) also results in T-cell activation, cytokine production, proliferation and differentiation. Natural killer (NK) cells are effector lymphocytes that play protective roles against both infectious pathogens and cancer. Dendritic cells (DC) are professional antigen presenting cells, able to induce naïve T cell activation and effector differentiation, involved in the induction and maintenance of immune tolerance in homeostasis. Tumor associated macrophages (TAMs) are constituted by: M1 macrophages that play critical roles in innate host defense by producing reactive oxygen/nitrogen species (ROS/RNS) and pro-inflammatory cytokines such as IL-1β, IL-6, tumor necrosis factor α (TNF-α), and M2 macrophages that produce anti-inflammatory cytokines such as IL-10, IL-13 and TGF-β to promote tumor development. Image created with BioRender.com.