Page 44 - Read Online

Page 4 of 17 Balakrishnan et al. J Cancer Metastasis Treat 2022;8:27 https://dx.doi.org/10.20517/2394-4722.2022.33

Figure 2. The immunosuppressive role of macrophages and myeloid-derived suppressor cells (MDSCs) in tumors. (A) The two
phenotypes of TAMs and their respective markers and functions. (B) TAM2 and MDSCs suppress tumor killing through five
immunosuppressive mechanisms: (i) via cell-to-cell contact, e.g., programmed cell death ligand-1(PD-L1) and cluster of differentiation
80 (CD80); (ii) secreted factors interleukin-10 (IL-10) and transforming growth factor-β (TGFβ); (iii) expression of enzymes arginase-1
(ARG1), inducible nitric oxide synthase (iNOS), and indoleamine 2,3 deoxygenase (IDO); (iv) engaging Tregs to aid in suppression by
expression of factors that stimulate differentiation (e.g., IDO, prostaglandin E2 (PGE2), IL-10, and TGFβ) or recruitment (e.g., CCL22);
and (v) interfering with TAM activity by suppressing the expression of IFN-γ and IL-12 which impact direct tumor killing and activation
[8,15,20-23]
of killer T cells .

tumor elimination by IFN-γ, IL-12, and IL-21 production [19,20] .

There are two types of DCs, known as conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs),
as shown in Figure 1. The cDCs are the dominant subset and are made up of two precursors, cDC1 and
cDC2; their respective markers are given in Table 2.

Notch signaling plays a role in DC differentiation, maturation, and activity as well [21-23] . Notch signaling
[24]
produces cDCs at higher yields from the HSCs . Out of the two precursors, cDC1 was shown to be an
important provider of chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 in tumor populations,