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Tumor Discovery Monocytes from single-cell analysis
surface to identify cell types or subtypes; therefore, it is hard In late monopoiesis, the bone marrow-derived monocytes
to purify cell clusters for further experiments. As reported can be divided into two subpopulations—“classical”
by some studies [7,8] , there are many methods that study the Ly6C CX3CR1 low (CCR2 CD62L ) and “nonclassical”
+
+
hi
behavior and phenotype of single cells, but these methods Ly6C CX3CR1 (CCR2 CD62L ) monocytes . In their
hi
low
−
−
[18]
do not seem to completely avoid the interactions between subsequent work, researchers demonstrated an intermediate
the single cells in further analyses , and these interactions cell state, which is Ly6C CD43 CX3CR1 in mice and
[9]
int
hi
hi
between individual cells should not be ignored. Under this CD14 CD16 in humans . The difference between the
[20]
+
+
circumstance, single-cell analysis techniques, including two subtypes is that Ly6 monocytes circulate in blood ,
[21]
low
single-cell RNA sequencing (scRNA-seq) and cytometry while classical inflammatory monocytes (CCR2 Ly6C in
hi
+
(CyTOF), were developed. These unbiased methods mice and CCR2 CD14 CD16 in humans) are recruited to
+
–
hi
enable more specific transcriptional and proteomic tumor sites where they increase the macrophage content and
profiling of different cell clusters at the single-cell level. promote tumor growth and metastasis . However, little is
[22]
Through single-cell genomics, we can easily determine known about whether this kind of classification corresponds
the level of gene expression of thousands of cells in a to the functional specialization of distinct subsets. Ly6C
+
single experiment without having to perform complex cell monocytes can be recruited and differentiated into
purification processes. This also helps with unbiased and macrophages or DCs in tissue, while Ly6C monocytes
−
precise classification of cell types and states, clustering and circulate in the blood and play a role as scavengers .
[23]
trajectory analysis as well as detection of genes that govern
cell state [10,11] . In contrast to traditional transcriptome Single-cell analysis is critical to providing new
analysis in which researchers extract bulk RNA from insights for studying human cancer. For example,
tissues and ultimately obtain average gene expression researchers can study the cell components in the complex
profiles, the scRNA-seq focuses on the heterogeneity of microenvironment of acute myeloid leukemia through
[24]
numerous cells. Thus, this recently developed technology scRNA-seq to investigate tumor progression . Zilionis
might provide us with new insights into monocytes. et al. recently uncovered 25 tumor-infiltrating myeloid
cells (TIMs) in non-small cell lung cancer patients using
ICB is beneficial to patients with diverse cancer types. single-cell transcriptomics methods, and also profiled
Consistent responses have been reported in patients with TIMs in mice. Compared to TIMs across species, they
advanced melanoma that received ICB as treatment , identified an almost congruence of population structures
[12]
thus prompting the trials of ICB to other cancers, including among DCs and monocytes, and found conserved
bladder cancer, non-small cell lung cancer, and Hodgkin’s neutrophil subsets and species differences among
lymphoma [13-15] . Despite the increase in overall survival in macrophages . Moreover, Puram et al. applied single-
[25]
33% – 40% of patients with melanoma, anti-PD-1 treatment cell transcriptomic analysis of nearly 6000 single cells
has not been found to be effective in most treated patients from 18 head and neck squamous cell carcinoma patients,
and has resulted in disease progression at a median follow-up refined the subtypes of tumors, and gave new insights into
of 21 months in 25% of patients [16,17] . Therefore, it is necessary the ecosystem .
[26]
to find biomarkers to identify individuals that are responsive
to clinical treatment. Of note, investigating the state of Cell subpopulations are traditionally defined according
monocytes and the single role of each subtype can be helpful for to a combination of morphology, localization, functions,
further study. In this review, we briefly summarize the recent ontogeny, and expression of a restricted set of molecular
findings about the classification and molecular mechanisms markers. The aforementioned classification of three types
of differentiation, interactions between monocytes and of monocytes (classical, nonclassical, and intermediate)
T lymphocytes and other components in TME, and how was first conducted in the late 1980s by using two-color
they influence the responsiveness of immunotherapies and flow cytometric detection of CD14 and CD16 antigens on
predict the prognosis of patients treated. human peripheral blood mononuclear cells (PBMCs) .
[27]
Single-cell transcriptional profiling has challenged our
2. Monocytes in human tumors understanding of heterogeneity in monocytes and other
[28]
2.1. Overview of monocytes states well-established immune cell populations . Single-cell
RNA sequencing can identify these cells easily and quickly
Monocytes are innate immune cells that patrol in the in an unbiased and precise way.
bloodstream and can be recruited into diverse tissues at an
increased rate during inflammation or tumorigenesis . Recent technological advances that allow single-
[18]
They are responsible for maintaining tissue homeostasis, cell analysis of phenotypic and transcriptional states
initiating host responses to pathogens, and involved in have revealed a vast heterogeneity of tumor-associated
immune responses (summarized in Table 1). monocytes/macrophages. Villani et al. revealed four
[19]
Volume 1 Issue 1 (2022) 2 https://doi.org/10.36922/td.v1i1.4

