Fig. 1

Schema interaction between tumor and immune cells. Full activation of T-lymphocytes requires the coordinated participation of several surface receptors on effector T cells and antigen-presenting cells (APCs) or tumor cells. The main route of T cell stimulation is driven by antigens recognized in the form of short polypeptides associated with MHC antigen-presenting molecules. However, the functional outcome of T cell stimulation towards clonal expansion and effector function acquisition is contingent on the contact of additional surface receptor-ligand pairs and on the actions of cytokines in the tumor microenvironment. While some of those interactions are inhibitory (in red), others are activating and are collectively termed co-stimulatory (in green) receptors. Communication between T cells and APCs is bidirectional. In some cases, this occurs when ligands themselves signal to the APC. In other cases, activated T cells upregulate ligands, such as CD40L, that engage cognate receptors on APCs. Tumor cells can upregulate PD-L1 expression via either the constitutionally activated oncogenic signaling (left, innate/intrinsic immune resistance) or the immune modulator-induced signaling pathways (right, adaptive immune resistance). Abbreviations: APC antigen-presenting cells, DC dendritic cell, IL-2R IL-2 receptor, MDSCs myeloid-derived suppressor cells, Teff effector T cell, Treg regulatory T cells, IDO indoleamin 2,3-dioxygenase, TIM-3 T cell immunoglobulin domain and mucin domain, LAG lymphocyte-activation gene, BTLA B- and T-lymphocyte attenuator, HVEM herpes virus entry mediator, TIGIT T cell immunoreceptor with Ig and ITIM domains, GITR glucocorticoid-induced tumor necrosis factor receptor, ICOS inducible costimulators, CEACAM carcinoembryonic antigen-related cell adhesion molecule, TSMA tumor-specific mutant antigens, JNK, c-Jun N-terminal kinase, MEK/ERK, mitogen/extracellular signal regulated kinase, PI3K, phosphatidylinositol 3-kinase, STAT, signal transducer and activator of transcription, NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells