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Tumor Discovery Monocytes from single-cell analysis

mammary tissue macrophages bear close resemblance to these immunosuppressive macrophages derived from
M2 macrophages . blood monocytes from other TAMs.
[64]
Murray et al. have proposed a common framework for TAM can be defined using MHCII, CD11c, and
macrophage activation nomenclature. TAMs are divided macrophage markers, and clustered with macrophages on
into eight subtypes, including M (IL-4), M (Ic), M (IL- transcriptional basis . Inflammatory cells and cytokines
[64]
10), M(GC+TGF-β), M (GC), M (LPS), M (LPS+IFN-γ), could play an important role in tumor progression
[17]
and M (IFN-γ). This nomenclature expanded the M1– and immunosuppression of some therapies . Fibiger
M2 definitions considering different activation scenarios et al. pointed out that chronic inflammatory irritation
(M2a, M2b, etc.) [103] . could trigger cancer development [110] . The functions of
Of note, there is a discrepancy between mouse and macrophages have been well documented; macrophages
human models of alternative activation [100] . In vitro produce angiogenic factors and growth factors that
macrophages are generated from monocytes after classical promote tumor invasion and metastasis. In tumors,
high
(LPS+IFN-γ) or alternative (IL-4) activation. In in vivo Ly6C monocytes exist as highly suppressive monocytic
and can
[111]
situations, these macrophages preferentially induce myeloid-derived suppressor cells (M-MDSC) [112]
the inducible nitric oxide synthase (iNOS) or arginase differentiate into TAMs and inflammatory DCs .
and are called M1 and M2. These two concepts are used 3.4.2. Monocytic DCs (moDCs)
interchangeably. However, a recent study pointed out
that M1(M2) in vivo was not equivalent to classically DCs arise from a common bone marrow progenitor — the
(alternatively) activated macrophages in vitro . Thus, common DCs progenitor (CDP) — and then differentiate
[66]
reliable markers of macrophage in vivo remain to be into pDCs and precursors for cDCs. Here, we chiefly
hi
identified. discuss the moDCs that originate from Ly6C monocytes
under the scenario of tumor or inflammation. Since TAMs
It is becoming clearer that the dichotomic polarization are the predominant component of TME, moDCs just
of pro-inflammatory M1 and anti-inflammatory M2 make up a minor fraction of tumor-infiltrated myeloid
cannot reflect the complexity of TME [104] . Actually, the cells. MoDCs play an anti-tumorigenic role mediated by
application of single cell transcriptome analysis helped some cytokines, including iNOS, TNF-α, IL-6, and IL-10,
determine that the states of all cell components (including which impede T cells proliferation in vitro [113] . However,
cancer cells, lymphocytes, and TAMs) in the TME may they can also efficiently engulf and process antigens and
span two extreme states [105] . Some findings challenged then activate CD8 T cell in several tumor models [114] . In
+
the common dogma of the M1/M2 classification of TAM. breast cancer models, DC populations were divided into
Through scRNA-seq, Elham et al. found that the gene “CD11b DC1” and “CD14 CD33 HLA-DR expression
+
+
–/lo
+
expression signatures of M1 and M2 macrophages were (CD11b Gr-1 Ly6C Ly6G cells in mice)” through an
+
+
+
–
positively related to the myeloid populations, and that the 11-color flow cytometry panel and progressive gating
macrophages differentiated in the same trajectory [104] . They strategy. CD103 DC2 showed unique antigen processing
+
found that TAMs might coexpress M1 and M2 markers and presentation capabilities [115] (summarized in Table 1).
instead of representing a mixture of M1 and M2 subsets,
indicating that human TAMs cannot be divided into M1 4. Targeting monocytes during clinical
and M2 in a conventional sense [106] . This finding, however, treatment for cancer
may controvert a previous theory that only polarization
of M1 and M2 exist. Recently, the heterogeneity of 4.1. Monocytes as diagnostic marker
TAMs in different tissues has been reviewed [107] . Resident Monocytes, TAMs, and moDCs may be promising
macrophages of TAMs can be divided into two subsets diagnostic markers for early diagnosis of some malignant
– resident macrophages derived from the embryo and tumors. Angiogenesis is a critical step in the development
those from the monocyte. This implies that monocyte- of HCC. As mentioned previously, TEMs are pro-
derived macrophage replaced the original models angiogenic. The levels of circulating TEMs were observed
(rapid in gut and dermis while slow in heart, lung, and to be significantly higher in HCC than in non-HCC
pancreas). Except for ontogeny of TAMs, the TME also patients. This implies that the level of circulating TEMs
induced some shared signatures of them [107] . In brain can be used as a diagnostic marker for HCC . This has
[85]
tumors, TAMs comprised microglial cells and monocytes, also been proven in a study that the TEMs percentage
which were also validated through scRNA-seq [108] . The in peripheral blood monocytes of 84 HCC patients who
two subtypes can be distinguished from each other by received hepatectomy was significantly increased. The
CD49d [109] . Thus, we may possibly identify and target study showed that the level of TEMs in peripheral blood

Volume 1 Issue 1 (2022) 8 https://doi.org/10.36922/td.v1i1.4