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Tumor Discovery Monocytes from single-cell analysis

and other monocytes-derived cells, thereby providing new whether M-MDSCs represent a terminally differentiated
clues for developing strategies for cancer immunotherapy. cell type rather than a cell state induced by cancer and other
pathologies requires further exploration. Monocytes and
3. Function of monocytes in tumors monocyte-derived cells interact with adaptive immunity

3.1. Recruitment to tumors and direct tumoricidal by regulating the recruitment and function of lymphocytes
function within the TME through paracrine signaling, as well as by
serving as antigen-presenting cells (APCs) .
[77]
C-C motif chemokine ligand 2 (CCL2) has been reported
to be a crucial mediator of monocyte recruitment during 3.2.2. Antigen-presenting function
tumorigenesis and metastasis in some cancer models, MPS-lineage cells, including monocytes, TAMs, and DCs,
including colorectal cancer (CRC) , breast cancer , and are thought to have the potential for antigen presentation
[30]
[69]
prostate cancer . CCL2 is also reportedly the main driver of due to their phagocytic capacity. While monocytes cannot
[70]
classical monocyte recruitment in the mouse model of bone function as APCs they may at least act as precursors of
metastasis of breast cancer. Instead of resident macrophages, TAMs and DCs in normal and dysfunctional tissues. Past
the recruited monocytes have been found to facilitate tumor studies have revealed their antigen presentation function
growth . Despite the great competence of migration during homeostasis and infection, while the role of tumor-
[71]
displayed by the bone marrow monocytes, the spleen has its derived antigen presentation remains unclear .
[77]
own group of monocytes. The spleen has also been recently
identified as a reservoir of monocytes. The removal of the Besides direct tumoricidal function, monocyte-derived
spleen, either before or after tumor initiation, significantly DCs (moDCs) can also serve as APCs in the tumor
reduced TAM responses and delayed tumor growth, context. In a recent study, anthracyclin chemotherapy
hi
+
+
indicating that the spleen was able to maintain its reservoir induced CD11c CD11b Ly6C cells at the tumor site
[78]
capacity throughout the course of tumor progression . by an ATP- and CCR2/CCL2-dependent mechanism .
[72]
Monocytes can kill tumor cells through cytokine-mediated Monocytes transferred into mice depleted of CD11c cells
+
cell death or phagocytosis. IFN-stimulated cells can produce were sufficient to rescue CD8 T cell priming in the lymph
+
[79]
TNF-related apoptosis-inducing ligand (TRAIL), which node and delayed tumor growth . Similarly, a population
hi
results in the apoptosis of some sensitive tumor cells, while of F4/80 monocyte-derived cells (with Mϕ phenotype but
other tumor cells can secrete more CCL2 and IL-8, thereby functional DC features) can efficiently cross-present tumor
[34]
+
promoting tumor development instead . Monocytes are also antigens to CD8 T cells . The underlying association
[53]
capable of antibody-dependent cytolysis and phagocytosis. between monocytes and T lymphocytes could be an
For instance, such function of CD16 monocytes is induced interesting research direction. Whether these interactions
+
by the TNF-α signaling pathway and direct contact with exist in the vasculature of tumors or even in the peripheral
tumor cells . circulation requires further exploration.
[73]
3.2. Interactions with lymphocytes 3.3. Interactions with other components in TME
3.2.1. Recruitment of lymphocyte 3.3.1. Angiogenesis
As forementioned, MDSCs can suppress the activation of Since the blood vessel delivers oxygen and nutrition to
CD4 and CD8 T cells. Here, we would like to summarize the neoplasm, angiogenesis is a necessary step for tumor
+
+
several main mechanisms associated with its suppressive progression. Pro-angiogenic monocytes and TAMs are
role. On the one hand, the uptake of arginine and high reported to regulate different processes of angiogenesis
intracellular levels of arginase lead to depletion of arginase, in gliomas, which are characterized by extensive neo-
[80]
which is a crucial amino acid for T cell activation [74,75] . angiogenesis . The formation of new vasculature requires
On the other hand, MDSCs also suppress the activation hypoxia-inducible factor (HIF)-mediated release of
of CD4 and CD8 T cells by downregulating the T cell chemokines and growth factors. In renal cell carcinoma
+
+
receptor-associated ζ-chain; this phenomenon is observed patients, peripheral blood CD14 monocytes produce
+
in most cancer patients and is caused by inflammation . vascular endothelial growth factor (VEGF) and facilitate
[76]
[76]
Both antigen recognition and signal transduction are angiogenesis through the NF-κB and IL-1-IL-1R axis .
[81]
+
crucial initial steps of antigen-specific immune responses. CD16 monocytes (or their progeny) release VEGF, and
Without the ζ-chain, T cells are unable to transmit the then generates a positive feedback loop that recruits more
required signals for activation. pro-angiogenic monocyte-derived cells.
However, the states of MDSC are not clearly identified In mouse models, a circulating monocyte subset
and many superficial markers and functions overlapped, thus expressing angiopoietin receptor TIE2 shows a pro-
Volume 1 Issue 1 (2022) 6 https://doi.org/10.36922/td.v1i1.4