Page 13 - TD-1-1

Tumor Discovery Monocytes from single-cell analysis

monocyte types after performing a single-cell RNA From the bone marrow, the progenitors give rise to
sequencing of ~2400 cells isolated from healthy blood circulating monocytes and their progeny, such as F4/80
low
donors and enrichment for HLA DR lineage cells . macrophages and DCs. The generation of macrophages
-
[29]
+
Among them, Mono1 and Mono2, as the two largest clusters, from fetal liver is unclear; however, these macrophages
contain the previously defined “classical” (CD14 CD16 ) may contribute to the evolution of Langerhans cells in
–
++
and “nonclassical” subtypes (CD14 CD16 ). Besides, adults .
[40]
++
+
these two subtypes also contain 88 of the 124 cells derived
from the “intermediate” monocyte gate (CD14 CD16 ). 2.2.2. DCs
++
+
Mono3 and Mono4, as the two additional clusters, include In mice, DCs and monocytes arise from a macrophage/
40 of the 124 “intermediate” cells and express some of the dendritic progenitor , which produces monocytes and a
[42]
Mono1 (classical monocyte) signature genes associated common dendritic progenitor (CDP) that is restricted to
with cell cycle, differentiation, and activation of NK and the DC fate. The CDP produces plasmacytoid DCs (pDCs)
T cells. The “intermediate” (CD14 CD16 ) monocytes and conventional DCs (cDCs), the latter of which leaves the
+
++
are usually distributed across the four types of monocytes. bone marrow and circulates in the blood before entering
[43]
However, it should be noted that more studies are needed tissues and developing into different DC subsets . The
to validate the existence and function of the two new previously identified subset of Ly6C monocytes expressed
+
clusters. For this heterogenous intermediate state, scRNA- DC-related genes that encode CD209a and MHC Class II
seq helps uncover a part of potential mechanisms related (MHCII), and granulocyte-macrophage CSF (GM-CSF)
+
to the differentiation, that is, CCAAT-enhancer-binding stimulates the differentiation of Ly6C monocytes into
[44]
protein beta (C/EBPβ), that activates a survival factor of DCs .
monocyte and thus promotes the differentiation of Ly6C 2.2.3. Myeloid-derived suppressive cells (MDSCs)
+
−
cells into Ly6C cells .
[23]
The concept of MDSCs was first suggested by Gabrilovichin
Both classical and non-classical monocytes can exhibit et al. in 2007 . This group of cells myeloid-lineage is
[45]
pro-tumoral or anti-tumoral functions in tumors. Of characterized by CD14 CD33 HLA DR expression
+
+
-
–/lo
note, classical monocytes differentiate into pro-tumoral (CD11b Gr-1 Ly6C Ly6G cells in mice) and their ability
+
+
+
–
TAMs [30,31] , inhibit function of T cells and contribute to suppress T cell function . In cancer patients, MDSCs
[32]
[46]
to angiogenesis , while monocytes can also be cytotoxic are typically CD11b CD33 CD34 CD14 HLA DR and
[22]
+
+
−
+
−
-
to tumor cells and facilitate antigen presentation . On their expression of CD15 and other markers are different
[34]
[33]
the other hand, non-classical monocytes mainly show between subtypes [47-49] . Of note, a new subpopulation of
anti-tumoral function, such as phagocytosis of tumor MDSC, CD14 HLA DR −/low , identified in melanoma and
-
+
[35]
material, prevention of tumor metastasis, and inhibition hepatocarcinoma patients is emerging. This indicates that
of Tregs . However, Tie-2 monocytes can also promote different subtypes of MDSC in human tumors are similar
[36]
+
angiogenesis in several tumors [37,38] . to those of tumors in mice [47,50] . MDSCs are immature
2.2. Origins and fates of monocytes and can be divided into monocytic (M-MDSC) and
granulocytic (G-MDSC) cells . Monocytes may develop
[51]
2.2.1. Macrophages into M-MDSCs, but monocytes cannot be distinguished
Macrophages develop from bone marrow stem cells, from M-MDSCs through markers. Increased G-MDSCs
[52]
and then go through their cell cycle as granulocyte- but not MMDSCs can be detected in many cancer types .
monocyte progenitor cells, pro-monocytes, and mature Inflammation promotes the accumulation of MDSCs
monocytes . Ly6C monocytes that patrol in the that down-regulates immune surveillance and antitumor
−
[39]
[17]
peripheral blood are responsible for detecting pathogens immunity, thereby facilitating tumor growth . C-C
and maintaining vascular integrity, while Ly6C monocytes chemokine receptor type 2 (CCR2) drives monocyte
+
are recruited to different tissues during infection or injury polarization to MDSCs and M2-like macrophages,
to mediate extravascular inflammatory responses. After thereby facilitating tumor growth in patients with lung
[53]
+
entering various tissues, Ly6C inflammatory monocytes adenocarcinoma .
differentiate into macrophages [40,41] . Macrophages in adults Understanding the origin and fate of monocytes will
derive from at least three origins, that is, yolk sac, fetal liver, help in understanding the function of monocytes in
and bone marrow. The progenitors in yolk sac populate tumors. The monocytes circulating in peripheral blood are
all tissues and form the F4/80 macrophage subtype in developed from common monocyte progenitor (cMoP),
hi
diverse tissues. In addition, resident macrophages are a lineage-committed bone marrow progenitor . In both
[54]
mainly regulated by colony stimulating factor 1 (CSF-1). mouse and human, cMoPs express stem cell marker
Volume 1 Issue 1 (2022) 4 https://doi.org/10.36922/td.v1i1.4