Page 21 - TD-1-1
P. 21

Tumor Discovery                                                         Monocytes from single-cell analysis



            used in different laboratories. Information pertaining to   and potential side effects of these therapeutic approaches
            the surface biomarkers overlapping between subsets and   are also important for future clinical applications.
            a unifying classification of monocytes, TAMs and moDCs
            based on ontogeny, location, function, and phenotype are   Funding
            urgently needed. Full delineation of the origin and function   This study was supported by grants from General Program,
            of TAMs, along with new pathways for the differentiation   The National Natural Science Foundation of China
            of TAMs can provide new insights into strategies of   (No. 81874138, 82073020 and 81903222).
            tumor immunotherapy [144] . Some concepts, such as TAM
            heterogeneity and the nature of the monocytic TAM   Conflict of interest
            precursors, are  speculative  and difficult  to  be  unified .   The authors declare no conflict of interest.
                                                        [22]
            Moreover, the ontogeny, transcriptional regulation, and
            heterogeneity of MPS remain largely unknown, which   Author contribution
            hampered their clinical application . Monocytes are
                                          [62]
            thought to preferentially generate immunosuppressive    Conceptualization: Mingzhu Yin
            TAMs in solid tumors, yet the basis for this is largely   Data curation: Xin Fu
            unknown . Moreover, monocytes can diversify into a   Writing - original draft: Xin Fu, Mingzhu Yin
                   [68]
            continuum of states, which may promote or impede tumor
            growth. More evidence is needed to determine whether   Writing - review & editing: Xin Fu, Mingzhu Yin.
            monocytes differentiate with intermediate modes of
            functioning. Conventional definitions of monocytes will   References
            likely be expanded, and new subpopulations of monocytes   1.   van Furth R, Cohn ZA, 1968, The origin and kinetics of
            and  intermediate  subsets  deserve  further  exploration   mononuclear phagocytes. J Exp Med, 128: 415–435.
            and to be identified . The mechanisms of tissue-specific      https://doi.org/10.1084/jem.128.3.415
                            [28]
            immunity and the basis of tumor immune escape still
            remain to be elucidated. In addition, the mechanisms of   2.   Engblom C, Pfirschke C, Pittet MJ, 2016, The role of myeloid
            balancing immune protection and self-tolerance and their     cells in cancer therapies. Nat Rev Cancer, 16: 447–462.
            correlation with tumor surveillance and escape are still not      https://doi.org/10.1038/nrc.2016.54
                          [59]
            well  documented .  The  clinical  studies  and  experiments   3.   Pollard JW, 2004, Tumour-educated macrophages promote
            in mouse models clearly indicate that TAMs show a pro-  tumour progression and metastasis.  Nat Rev Cancer,
            tumoral phenotype that facilitates tumor cell invasion,   4: 71–78.
            motility, and intravasation. Therefore, it is not surprising      https://doi.org/10.1038/nrc1256
            that extensive TAM infiltration is positively associated with
            cancer metastasis and poor clinical prognosis in various   4.   Sica A, Schioppa T, Mantovani A,  et al., 2006, Tumour-
            human cancers [145] . As for treatment for malignancy, early   associated macrophages are  a distinct  M2 polarised
                                                                  population promoting tumour progression: Potential targets
            diagnosis and screening for high-responsive patients for   of anti-cancer therapy. Eur J Cancer, 42: 717–727.
            immunotherapies are key to be part of prophylactic approach
            and effective treatment. One of the future directions is to      https://doi.org/10.1016/j.ejca.2006.01.003
            unveil the underlying functions of mononuclear phagocytes   5.   Yunna C, Mengru H, Lei W, et al., 2020. Macrophage M1/
            and their potential as diagnostic and therapeutic targets.   M2 polarization. Eur J Pharmacol, 877: 173090.
            Besides, combination therapy targeting monocytes and      https://doi.org/10.1016/j.ejphar.2020.173090
            immune checkpoint therapy may be promising.
                                                               6.   Krieg C, Nowicka M, Guglietta S,  et al., 2018, High-
              Most patients do not show durable responses to      dimensional  Single-cell  Analysis  Predicts  Response  to
            immunotherapy, especially ICT, despite a dramatic     Anti-PD-1 Immunotherapy. Nat Med, 24: 144–153.
            increase in progression-free survival. Therefore, more      https://doi.org/10.1038/nm.4466
            accurate biomarkers of the clinical response to ICT are
            urgently needed. In addition, it is still not clear how these   7.   Roberts SA, Waziri AE, Agrawal N, 2016, Development of
            APCs develop and function before and during anti-PD-1   a single-cell migration and extravasation platform through
            ICB or how they are associated with tumor rejection [130] .   selective surface modification. Anal Chem, 88:2770–2776.
            The  functions  of  monocytes in  ICB  therapy  and  other      https://doi.org/10.1021/acs.analchem.5b04391
            immunotherapies require further exploration because they   8.   Chen YC, Allen SG, Ingram PN,  et al., 2015, Single-cell
            are quite promising targets for the diagnosis and treatment   migration chip for chemotaxis-based microfluidic selection
            of human cancers. In addition, the benefits, limitations,   of heterogeneous cell populations. Scientific reports, 5: 9980.


            Volume 1 Issue 1 (2022)                         12                        https://doi.org/10.36922/td.v1i1.4
   16   17   18   19   20   21   22   23   24   25   26