1. Figure 4 Combination immunotherapeutic approaches with imatinib
Figure 4 | Combination immunotherapeutic approaches with imatinib. Several complementary treatment approaches could be envisioned in combination with first-generation or second-generation tyrosine kinase inhibitors (TKIs). The T-cell arm of immune responses could be ameliorated with peptide-based or protein-based vaccines, with immune-checkpoint inhibitors (such as the anti-cytotoxic-T-lymphocyte-associated-antigen-4 antibody ipilimumab, which depletes TREG cells in the tumour), with dendritic cell (DC) growth factors (such as FLT3L) and DC adjuvants (such as Toll-like receptor (TLR) agonists, anti-CD40 agonistic antibodies, or others). The natural killer (NK)-cell arm of immunity could be boosted with NK-cell-stimulatory cytokines (such as IL-15 or type I interferon), with anti-KIR antibody or anti-IL-10 antibody, mostly in patients with an unfavourable NKp30 isoform profile. Chimeric antigen receptor (CAR) T cells can be engineered to express the extracellular domain of NKp30 or antibodies recognizing B7-H6 to promote killing of cells expressing NKp30 ligands and B7-H6, respectively. Blocking indoleamine 2,3-dioxygenase (IDO) enzymatic activity or reprogramming M2-type tumour-associated macrophages (TAM) using anti-CSF1R (macrophage colony-stimulating factor 1 receptor) or small-molecule inhibitors of CSF1R signalling could be instrumental in preventing the proangiogenic and/or profibroblastic effects of TAM after TKI therapy. ICB, immune checkpoint blockade; KIR, killer IgG-like receptor.
Kroemer, G. et al. (2016) Immunological off-target effects of imatinib
Nat. Rev. Clin. Oncol. doi: /nrclinonc