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Tumor Discovery Monocytes from single-cell analysis

of other immunotherapies [139] . Taken together, monocytes of BET family proteins is widely studied for devising
and their derived APCs are critical to the response of cancer treatment. Yin et al. discovered a BET inhibitor
anti-PD-1 therapy and could serve as a potential target for (NHWD-870), which impedes the proliferation of
combination therapy. TAMs in mouse models and has better potency and
bioavailability than some BET inhibitors currently in
4.3.3. ICB induces remolding of monocytes/ clinical stage. One of the potential mechanisms is that
macrophages NHWD-870 inhibits BRD4 and its target HIF1α, and then
Devalaraja et al. studied several solid tumor models reduces the expression of macrophage CSF-1 [141] . Different
and revealed that IL-13 in the TME induced cancer subpopulations of monocytes possess different roles in
cells to produce RA, resulting in the differentiation of tumor metastasis. Transferring of Ly6Clo monocytes into
monocytes toward immunosuppressive TAMs rather Nr4a1-deficient mice that lack Ly6Clo monocytes led to
[68]
than immunostimulatory DCs . In addition, they reduced tumor metastasis by nearly four-fold in a mouse
[35]
generated Raldh1/3 double knockout (DKO) mice which model of melanoma metastasis to the lung . On the
showed >80% reduction in Raldh1 and Raldh3 transcripts, contrary, adoptive transfer of Ly6Chi monocytes led to
and found that F4/80 TAMs from DKO tumors were almost doubled tumor metastasis, which is consistent with
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significantly less suppressive to T cell proliferation and their pro-tumoral role. This indicates that intravascular
activation ex vivo. This indicates that the inhibitory role is adoptive transfer of anti-tumor monocytes might be a
probably confined to within the TME. potential treatment strategy. However, CAR T cell therapy
has received great success in the clinical treatment of some
Although ICT is designed to target lymphoid cells, it [142]
is also related to the remodeling of the TME. Monocytes/ hematological malignancies , and the application of
transferring monocytes has faced with the challenge that
macrophages that infiltrated into the TME constitute the their proliferative capacity ex vivo is limited, rendering
largest group in the scRNA-seq tSNE plots and undergo a gene editing difficult. Nevertheless, several clinical trials
markable remodeling during the ICT. Using scRNA-seq and on patients with recurrent chemotherapy-resistant ovarian
CyTOF, Gubin et al. discovered macrophage remodeling cancer are now underway [143] . Results from this clinical
during the ICT; these macrophages, which were derived trial will be informative for future directions in monocyte
from the T3 tumor mouse model, could be divided into transfer therapy.
five and eight subpopulations, respectively, according
to the technique used. In addition, they also studied the 5. Challenges and prospects
polarization process and found that 7 – 9 days after ICB or
control antibody treatment showed a branch point. Then, This review briefly introduces the traditional monocyte
they conducted a parallel cohort of monoclonal antibody states and new findings of the classification of monocytes
and ICT treatment along with the inhibition of IFN-γ. and their derived mononuclear phagocytes, including
On day 7, the proportion of iNOS cells in CD45 cells macrophage, moDC and MDSC. These cells are reportedly
+
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increased 11.4-fold from 1.2% at the baseline to 13.7%, crucial in tumor proliferation and metastasis due to their
compared to the group treated with anti-mouse IFN-γ correlation with other components in TME. Single-cell
monoclonal antibody increased 7.3-fold. This indicates analysis is used to identify the subsets and differentiation
one of the possible differentiation mechanisms, that is, the trajectories of monocytes through accurate profiling of
generation of an abundance of iNOS pro-inflammatory each single cell and to verify previous assumptions.
+
macrophages induced by the cytokine (IFN-γ) released by Over the last decade, studies have gradually found out
the reinvigored T cells in ICT [140] . They found increased the heterogeneity of MPS and the diverse functions facing
CD206 expression in the monoclonal antibody-treated different stimuli. We now realize that monocytes are
mice and increased iNOS expression in the ICT-treated collectively a heterogenous population . However, the
[28]
mice. Taken together, ICT leads to a change in the nomenclature of monocytes has always been a challenge
macrophages that play an immunosuppressive role and for researchers. Despite the much improved techniques at
favor tumor growth during ICT in a manner partially the single-cell level that are used for the classification of
dependent on IFN-γ [140] . system (MPS), there still exist many miscommunication
and confusion due to the lack of unifying nomenclature.
4.3.4. Potential application in other therapies We consider a systematic classification system coupled with
The function and interactions of monocytes in ICB naming convention to be important because each single
reflect their important role in TME. Several studies subset implies a functional specialization. Therefore, it is
have demonstrated the potency of targeting monocytes important for us to demarcate new subsets in the immune
to inhibit tumor growth and metastasis. Inhibition system and establish standardized system, which will be

Volume 1 Issue 1 (2022) 11 https://doi.org/10.36922/td.v1i1.4