Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment
Cancer is the leading cause of death globally superseded only by cardiovascular diseases, and novel strategies to overcome therapeutic resistance against existing cancer treatments are urgently required. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with potent immunosuppressiv...
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| Format: | Article |
| Language: | English |
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Open Exploration Publishing Inc.
2024-02-01
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| Series: | Exploration of Targeted Anti-tumor Therapy |
| Subjects: | |
| Online Access: | https://www.explorationpub.com/Journals/etat/Article/1002212 |
| _version_ | 1797292818869256192 |
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| author | Eric Jou Natasha Chaudhury Fizza Nasim |
| author_facet | Eric Jou Natasha Chaudhury Fizza Nasim |
| author_sort | Eric Jou |
| collection | DOAJ |
| description | Cancer is the leading cause of death globally superseded only by cardiovascular diseases, and novel strategies to overcome therapeutic resistance against existing cancer treatments are urgently required. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with potent immunosuppressive capacity against well-established anti-tumour effectors such as natural killer cells (NK cells) and T cells thereby promoting cancer initiation and progression. Critically, MDSCs are readily identified in almost all tumour types and human cancer patients, and numerous studies in the past decade have recognised their role in contributing to therapeutic resistance against all four pillars of modern cancer treatment, namely surgery, chemotherapy, radiotherapy and immunotherapy. MDSCs suppress anti-tumour immunity through a plethora of mechanisms including the well-characterised arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS)-mediated pathways, along with several other more recently discovered. MDSCs are largely absent in healthy homeostatic states and predominantly exist in pathological conditions, making them attractive therapeutic targets. However, the lack of specific markers identified for MDSCs to date greatly hindered therapeutic development, and currently there are no clinically approved drugs that specifically target MDSCs. Methods to deplete MDSCs clinically and inhibit their immunosuppressive function will be crucial in advancing cancer treatment and to overcome treatment resistance. This review provides a detailed overview of the current understandings behind the mechanisms of MDSC-mediated suppression of anti-tumour immunity, and discusses potential strategies to target MDSC immunosuppressive mechanisms to overcome therapeutic resistance. |
| first_indexed | 2024-03-07T20:02:03Z |
| format | Article |
| id | doaj.art-561015cff8ce4fcb9fba17fcaa000dd0 |
| institution | Directory Open Access Journal |
| issn | 2692-3114 |
| language | English |
| last_indexed | 2024-03-07T20:02:03Z |
| publishDate | 2024-02-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Targeted Anti-tumor Therapy |
| spelling | doaj.art-561015cff8ce4fcb9fba17fcaa000dd02024-02-28T05:55:59ZengOpen Exploration Publishing Inc.Exploration of Targeted Anti-tumor Therapy2692-31142024-02-015118720710.37349/etat.2024.00212Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatmentEric Jou0https://orcid.org/0000-0002-6259-4874Natasha Chaudhury1Fizza Nasim2Medical Sciences Division, Oxford University Hospitals, University of Oxford, OX3 9DU Oxford, UK; Kellogg College, University of Oxford, OX2 6PN Oxford, UK; Wexham Park Hospital, Frimley Health NHS Foundation Trust, SL2 4HL Slough, UKWexham Park Hospital, Frimley Health NHS Foundation Trust, SL2 4HL Slough, UKWexham Park Hospital, Frimley Health NHS Foundation Trust, SL2 4HL Slough, UKCancer is the leading cause of death globally superseded only by cardiovascular diseases, and novel strategies to overcome therapeutic resistance against existing cancer treatments are urgently required. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with potent immunosuppressive capacity against well-established anti-tumour effectors such as natural killer cells (NK cells) and T cells thereby promoting cancer initiation and progression. Critically, MDSCs are readily identified in almost all tumour types and human cancer patients, and numerous studies in the past decade have recognised their role in contributing to therapeutic resistance against all four pillars of modern cancer treatment, namely surgery, chemotherapy, radiotherapy and immunotherapy. MDSCs suppress anti-tumour immunity through a plethora of mechanisms including the well-characterised arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS)-mediated pathways, along with several other more recently discovered. MDSCs are largely absent in healthy homeostatic states and predominantly exist in pathological conditions, making them attractive therapeutic targets. However, the lack of specific markers identified for MDSCs to date greatly hindered therapeutic development, and currently there are no clinically approved drugs that specifically target MDSCs. Methods to deplete MDSCs clinically and inhibit their immunosuppressive function will be crucial in advancing cancer treatment and to overcome treatment resistance. This review provides a detailed overview of the current understandings behind the mechanisms of MDSC-mediated suppression of anti-tumour immunity, and discusses potential strategies to target MDSC immunosuppressive mechanisms to overcome therapeutic resistance.https://www.explorationpub.com/Journals/etat/Article/1002212tumor microenvironmentcancer therapypreclinical modelsimmunotherapymyeloid-derived suppressor cellmyeloid cellsimmunosuppression |
| spellingShingle | Eric Jou Natasha Chaudhury Fizza Nasim Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment Exploration of Targeted Anti-tumor Therapy tumor microenvironment cancer therapy preclinical models immunotherapy myeloid-derived suppressor cell myeloid cells immunosuppression |
| title | Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment |
| title_full | Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment |
| title_fullStr | Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment |
| title_full_unstemmed | Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment |
| title_short | Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment |
| title_sort | novel therapeutic strategies targeting myeloid derived suppressor cell immunosuppressive mechanisms for cancer treatment |
| topic | tumor microenvironment cancer therapy preclinical models immunotherapy myeloid-derived suppressor cell myeloid cells immunosuppression |
| url | https://www.explorationpub.com/Journals/etat/Article/1002212 |
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