Figure 1.

Immunological effects of chemotherapy, radiotherapy, and checkpoint inhibitors. Cyclophosphamide induces ICD which enhances the recruitment, activation, maturation, and antigen uptake by DCs. In addition, cyclophosphamide and temozolomide deplete Tregs and induce lymphoablation upon treatment with low-dose or high-dose, respectively. Immunological functions of gemcitabine entail depletion of Tregs and MDSCs. Radiotherapy induces, besides ICD, enhanced expression of FAS, MHC class I, and NKG2D ligands on tumor cells and enhanced expression of VCAM-1 on endothelial cells. Furthermore, secretion of CXCL16 by tumor cells is increased after radiotherapy. Antagonistic CTLA-4 antibodies enhance T-cell activation by the preventing the binding of CD28 with CD80/86. Ipilimumab depletes Tregs by ADCC whereas tremelimumab inhibits functions of Tregs upon binding. Anti-PD1 antagonistic antibodies enhance T-cell effector functions while preventing exhaustion of T-cells. Blockade of PD-1 on DCs improves survival while blockade of PD-L on tumor cells results in improved tumor-cell infiltration and killing. Ab, antibody; Ag, antigen; ATP, adenosine triphosphate; CALR, calreticulin; CTLA-4, cytotoxic T-lymphocyte-associated antigen; CXCL16, chemokine ligand 16; DC, dendritic cell; Fas, first apoptosis signal; HMGB1, high mobility group box 1; MDSC, myeloid-derived suppressor cell; MHC class I/II, major histocompatibility complex class I/II; NKG2D ligand, natural killer group 2 member D; PD-1, programmed death 1; PD-L, programmed death ligand; TCR, T-cell receptor; Treg, regulatory T cell; VCAM-1, vascular endothelial cell adhesion protein 1.