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Balakrishnan et al. J Cancer Metastasis Treat 2022;8:27 https://dx.doi.org/10.20517/2394-4722.2022.33 Page 3 of 17

Table 1. Function of factors that are produced by tumor cells
Factors Function
GM-CSF • Myelopoiesis and DC differentiation [102]
G-CSF • Differentiation, proliferation and survival of granulocytes [102]
[8]
• Downregulates Interferon regulatory factor - 8 (IRF8) in DC progenitors, and thus results in reduced DC development
[8]
• More recruitment of MDSCs
[8]
• Mobilize granulocytic myeloid cells from the bone marrow to promote angiogenesis
[102]
M-CSF • Differentiation, proliferation and survival of macrophages
• Suppresses the differentiation of DCs while enhancing TAM2 polarization [103]
VEGF • Promoting angiogenesis

Figure 1. Myeloid cells in the tumor microenvironment. Myeloid cell differentiation induced by persistent stimulation with tumor-
[8]
derived factors from hematopoietic stem cells (HSCs) . In the presence of normal activation signals (such as G-CSF, GM-CSF, Flt3-L,
[8]
CCL2, VEGF, and S100A8/9 ), the monocytes and granulocyte progenitors undergo terminal differentiation to form mature
macrophages, DCs, or granulocytes. Induction of an alternative activation pathway induces the formation of tumor-associated
macrophages (TAMs), DCs, myeloid-derived suppressor cells (MDSCs), and tumor-associated neutrophils (TANs). The markers of
these myeloid cells are also indicated in the figure.

such as the presence of lactate, extracellular adenosine, and hypoxia in TME affect the ability of DCs to
present antigens, which eventually hampers adaptive immunity . Thus, it can be seen that factors secreted
[17]
by the tumor shape TME and skew the function of myeloid cells strategically to facilitate immune evasion.
Further sections in this article discuss the myeloid cells present in TME and how they impact tumor
therapy.

Dendritic cells
Dendritic cells (DCs) are versatile antigen-presenting cells and serve to prime naïve T cell response. A
decline in DC functions contributes to tumor immune evasion and compromised cell-mediated immune
response in tumors . DCs present tumor antigens to T cells in an immunogenic context by the production
[18]
of cytokine interleukin 12 (IL-12p70), which induces T-helper (Th1) lineage commitment and subsequent