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Tumor Discovery Monocytes from single-cell analysis

may be applied as a biomarker for identifying HBV-related Blocking PD-1/PD-L1 through monoclonal antibodies
HCC [116] . has shown outstanding clinical efficacy in patients with
various tumors [13-15,131] . It has been reported that the testing
4.2. Monocytes as therapeutic targets of anti-PD-1 antibody lambrolizumab in patients with

At present, the use of monoclonal antibodies small- advanced melanoma led to a high rate of durable tumor
molecule inhibitors, and RNA interference techniques regression [132] . However, Topalian et al. pointed out that
targeting CCL2 and CSF-1 signaling pathways, which are the objective responses produced by anti-PD-1 antibody
responsible for recruitment of TAMs from circulating (BMS-936558) occurred in approximately one out of four
blood into the TME, is being studied [117] . The clinical trial to five patients with non-small-cell lung cancer, melanoma,
[12]
of the combination of CSF-1R and PD-1 blockade therapy or renal cell cancer .
in pancreatic cancer patients is currently at phase II . Das et al. introduced a cancer-specific prognostic
[95]
CCL2 blockade combination therapies led to elevated immune score model based on the analysis of immune
responsiveness in pancreatic cancer patients [118] . However, function-related genes from four single-cell RNA-Seq data
this may result in an infiltration of an abundance of sets and 20 bulk tumor RNA-Seq data sets. They revealed
monocytes into the TME from bone marrow, which has that the immune score models can predict disease-free and
been found to increase metastasis in a breast cancer mouse overall survival for 20 types of cancers. Besides, the models
model [119] . Besides, alternative strategies could directly target can also predict response to immunotherapies in some
immune suppressive TAM effector molecules, such as Arg1 specific cancers [133] .
inhibitors [119] . Strategies to deplete pro-tumorigenic TAMs
Although immune-checkpoint cancer therapy (ICT)
or to convert TAMs are needed. In addition, exploring shows encouraging results in many types of cancers,
specific markers can also enhance the efficacy of therapy. its effect is still limited. The reason why the efficacy of
Therapies can target the process of MDSC formation in the immunotherapy varies among different tumor types
bone marrow [120] , their recruitment to tumor site [121] , and is probably due to heterogeneity of the immune cell
some immune suppressive activities induced by MDSCs [122] .
composition in individual tumors [104] . It is universally
4.3. Monocytes and immune checkpoint therapy known that TAM is an important component of TME.
Devalaraja et al. found that monocytes and TAMs are a
4.3.1. Function of monocytes in immune checkpoint major part of intratumoral leukocytes in the three sarcoma
therapy models . The effects of immunotherapy, to some degree,
[68]
Current efforts focus on the combination therapies of are impeded by immunosuppressive TME. Cytokines in
blocking immune inhibitory pathways and immune the TME promote the differentiation of suppressive TAMs
stimulatory co-receptors to improve the responsiveness and inhibit DCs, hampering the function of cytotoxic anti-
to these two kinds of ICB therapies [123] . Tumors tumor T cells [114] . As mentioned before, tumor-educated
exploit multiple mechanisms, including local immune TAMs facilitate tumor progression and metastasis through
[3]
suppression, tolerance, and systemic T cell dysfunction cytokines in the TME . In return, TME is likely assumed
states, to evade intrinsic immune system or to resist to be altered by intratumoral monocytes and TAM, which
immunotherapies [124-126] . Blocking T cell coinhibitory is the main component of tumor stroma.
molecules, including cytotoxic T lymphocyte-associated 4.3.2. Monocytes as a predictive marker for response
protein 4 (CTLA-4), PD-1 or its ligand (PD-L1), have to ICB therapy
displayed durable anti-tumor efficacy and relatively
longer clinical remissions in patients with either solid or (A) Level of monocyte predicts responsiveness to anti-PD-1
hematological tumors [127] . therapy
PD-1 is an inhibitory receptor expressed on the surface Due to the variable efficacy of ICT and the extremely high
of T cells, and PD-L1 is expressed on the surface of various costs, it is critical to assess the condition of individuals
other cell types, including tumor cells and myeloid cells [128] . and avoid wasting time in treatment. Therefore, many
Anti-PD-1 therapy aims to dampen the interaction researchers are devoted to finding reliable predictive
between tumor-reactive T cells and tumor cells by blocking biomarkers, which can be used to filter patients who
PD-L1 and/or PD-L2/PD-1 signaling pathways [129] . To be have good responsiveness to anti-PD-1 therapy before
exact, the inhibitory checkpoint receptor PD-1 was found application and to predict progression-free survival and
to impede cytotoxic CD8 T cells in TME [130] . In addition, reduce the chance of relapse.
+
tumor cells frequently overexpress PD-L1, helping itself Krieg et al. studied the PBMCs isolated from 20 patients
to escape from the surveillance of the immune system. with melanoma and ten healthy people, which were

Volume 1 Issue 1 (2022) 9 https://doi.org/10.36922/td.v1i1.4