A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment

Hofer, Francesca; Sario, Gianna Di; Musiu, Chiara; Sartoris, Silvia; Sanctis, Francesco De; Ugel, Stefano

doi:10.3390/cells10102700

Cited by 38 publications

(25 citation statements)

References 257 publications

(327 reference statements)

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“…In the early 2000s, before the term MDSC was generated, vitamin D and all-trans retinoic acid (ATRA) were shown to reduce immature myeloid cells in patients with head and neck squamous cell carcinoma and metastatic renal cell carcinoma, respectively. 489 Currently, MDSC-targeted therapy can be broadly classified into five types: (i) therapies that inhibit the expansion and recruitment of MDSCs; (ii) therapies that restore normal myeloid differentiation; (iii) therapies that target the IC molecules on MDSCs; (iv) therapies that block the inhibitory molecules secreted from MDSCs; and (v) therapies that directly deplete MDSCs. 480 , 490 Since the enrichment and activation of MDSCs appear to be universal features of different malignancies, targeting these cells may have broader application potential.…”

Section: Targeting the Suppressive Tmementioning

confidence: 99%

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Wang

Sun

2022

Sig Transduct Target Ther

178

114

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Cancers are highly complex diseases that are characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming of the immune system play critical roles in tumor initiation and progression. Immunotherapy aims to reactivate antitumor immune cells and overcome the immune escape mechanisms of tumors. Represented by immune checkpoint blockade and adoptive cell transfer, tumor immunotherapy has seen tremendous success in the clinic, with the capability to induce long-term regression of some tumors that are refractory to all other treatments. Among them, immune checkpoint blocking therapy, represented by PD-1/PD-L1 inhibitors (nivolumab) and CTLA-4 inhibitors (ipilimumab), has shown encouraging therapeutic effects in the treatment of various malignant tumors, such as non-small cell lung cancer (NSCLC) and melanoma. In addition, with the advent of CAR-T, CAR-M and other novel immunotherapy methods, immunotherapy has entered a new era. At present, evidence indicates that the combination of multiple immunotherapy methods may be one way to improve the therapeutic effect. However, the overall clinical response rate of tumor immunotherapy still needs improvement, which warrants the development of novel therapeutic designs as well as the discovery of biomarkers that can guide the prescription of these agents. Learning from the past success and failure of both clinical and basic research is critical for the rational design of studies in the future. In this article, we describe the efforts to manipulate the immune system against cancer and discuss different targets and cell types that can be exploited to promote the antitumor immune response.

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Section: Targeting the Suppressive Tmementioning

confidence: 99%

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Wang

Sun

2022

Sig Transduct Target Ther

178

114

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“…The recent decades witnessed the bloom of tumor immunotherapy [ 1 , 2 , 3 ]. The central aim of immunotherapy is to harness autologous immune responses for tumor elimination [ 1 , 4 , 5 , 6 , 7 , 8 ]. Distinct from conventional approaches such as surgery, chemotherapy, and radiotherapy, the modulation of the immune system can lead to abscopal and long-lasting therapeutic consequences, therefore preventing tumor recurrence and metastasis [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Small-Molecule PROTACs for Cancer Immunotherapy

Liu¹,

Zhang²,

Xiang³

et al. 2022

Molecules

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Unsatisfactory physicochemical properties of macromolecular drugs seriously hinder their application in tumor immunotherapy. However, these problems can be effectively solved by small-molecule compounds. In the promising field of small-molecule drug development, proteolysis targeting chimera (PROTAC) offers a Cancer Patients. Bosn. J. Basic novel mode of action in the interactions between small molecules and therapeutic targets (mainly proteins). This revolutionary technology has shown considerable impact on several proteins related to tumor survival but is rarely exploited in proteins associated with immuno-oncology up until now. This review attempts to comprehensively summarize the well-studied and less-developed immunological targets available for PROTAC technology, as well as some targets to be explored, aiming to provide more options and opportunities for the development of small-molecule-based tumor immunotherapy. In addition, some novel directions that can magnify and broaden the protein degradation efficiency are mentioned to improve PROTAC design in the future.

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“…MDSCs are a differentiated type of myeloid cells that can be divided into three major subpopulations in humans: monocytic (M)-MDSCs (CD14 + CD15 − HLA-DR lo/ − cells), polymorphonuclear (PMN)-MDSCs (CD11b + CD14 − CD15 + CD66b + low-density cells), and early-MDSCs (Lin − CD11b + CD34 + CD33 + CD117 + HLA-DR lo/ − cells) ( 82 ). MDSCs have been found in association with various human cancer tissues, where they can act as an independent prognostic factor for the overall survival rate ( 83 ).…”

Section: Lipid Metabolism Reprogramming Of Various Immunocytes In The...mentioning

confidence: 99%

Targeting lipid metabolism reprogramming of immunocytes in response to the tumor microenvironment stressor: A potential approach for tumor therapy

et al. 2022

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The tumor microenvironment (TME) has become a major research focus in recent years. The TME differs from the normal extracellular environment in parameters such as nutrient supply, pH value, oxygen content, and metabolite abundance. Such changes may promote the initiation, growth, invasion, and metastasis of tumor cells, in addition to causing the malfunction of tumor-infiltrating immunocytes. As the neoplasm develops and nutrients become scarce, tumor cells transform their metabolic patterns by reprogramming glucose, lipid, and amino acid metabolism in response to various environmental stressors. Research on carcinoma metabolism reprogramming suggests that like tumor cells, immunocytes also switch their metabolic pathways, named “immunometabolism”, a phenomenon that has drawn increasing attention in the academic community. In this review, we focus on the recent progress in the study of lipid metabolism reprogramming in immunocytes within the TME and highlight the potential target molecules, pathways, and genes implicated. In addition, we discuss hypoxia, one of the vital altered components of the TME that partially contribute to the initiation of abnormal lipid metabolism in immune cells. Finally, we present the current immunotherapies that orchestrate a potent antitumor immune response by mediating the lipid metabolism of immunocytes, highlight the lipid metabolism reprogramming capacity of various immunocytes in the TME, and propose promising new strategies for use in cancer therapy.

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A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment

Cited by 38 publications

References 257 publications

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Small-Molecule PROTACs for Cancer Immunotherapy

Targeting lipid metabolism reprogramming of immunocytes in response to the tumor microenvironment stressor: A potential approach for tumor therapy

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