Table 1 Overview of strategies to target myeloid cells in AML.
From: Targeting the innate immune system in pediatric and adult AML
Strategies | Targets |
|---|---|
Deplete myeloid cells | • Targeting CCL2/CCR2 and M-CSF/M-CSFR pathways to inhibit monocytes recruitment to the tumor site and TAM maintenance; • Blocking CXCL8 or CXCR1 and CXCR2 to inhibit neutrophils mobilization and recruitment; • Interfering with VEGF-VEGFR signaling, contributing to TIMs migration and differentiation. |
Reprogram myeloid cells into antitumor effectors | • Triggering TLRs: increased immunogenicity (DCs and NKs activation, conversion from M2-like to M1-like macrophages); • Cytokines: IL-12 associated with reprogramming of MDSCs, DCs, and TAMs; • Manipulation of transcription factors: STAT3, NF-kB and PI3Kγ; • Inhibition of enzymes expressed by TIMs (IDO-1, ARG-1, iNOS). |
Targeting cell surface receptors | • “Don’t eat me signals”: CD47/SIRPα, CD24/SIGLEC10 • Activating receptors: CD40/CD40L • Immune checkpoint inhibitors on macrophages |
