MDSCs might be “Achilles heel” for eradicating CSCs

Yang, Tao; Liang, Ning; Li, Jing; Hu, Pan; Huang, Qian; Zhang, Zhao; Wang, Qian

doi:10.1016/j.cytogfr.2022.04.006

Cited by 9 publications

(4 citation statements)

References 109 publications

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“…As shown in Figure A,B, DPP greatly decreased the fluorescence intensity, while CDDP increased the fluorescence intensity in the tumor tissue, suggesting that the infiltration of intratumor MDSCs was inhibited by DPP but stimulated by CDDP. Arg-1 plays a vital role in promoting the proliferation and activation of MDSCs to form an immunosuppressive TME. , The expression of Arg-1 in tumor tissues of mice was detected by immunochemistry analysis. As shown in Figure C, DPP markedly lowered the expression of Arg-1 (brown).…”

Section: Resultsmentioning

confidence: 99%

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Platinum(IV) Complexes as Inhibitors of STAT3 and Regulators of the Tumor Microenvironment To Control Breast Cancer

Cai,

Wang,

Chen

et al. 2023

J. Med. Chem.

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Interplay between breast cancer (BC) cells and the tumor microenvironment (TME) influences the outcome of cancer treatment. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) promotes the interaction and causes immunosuppression and drug resistance. Platinum(IV) complexes SPP and DPP bearing pterostilbene-derived axial ligand(s) were synthesized to inhibit the JAK2-STAT3 pathway in BC cells and regulate the TME. These complexes exerted remarkable antiproliferative activity against the triple-negative BC cells, suppressed the expression of phosphorylated STAT3 and STAT3-related cyclooxygenase-2 and IL-6, and activated caspase-3 and cleaved poly ADP-ribose polymerase, preventing the repair of DNA lesions and inducing apoptosis. Furthermore, DPP promoted the maturation and antigen presentation of dendritic cells, repressed the proliferation and differentiation of myeloid-derived suppressor cells and regulatory T cells, and facilitated the expansion of T cells. As a consequence, DPP showed excellent anticancer activity against BC with almost no general toxicity in vivo as a potential chemoimmunotherapeutic agent.

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Section: Resultsmentioning

confidence: 99%

“…Arg-1 plays a vital role in promoting the proliferation and activation of MDSCs to form an immunosuppressive TME. 64,65 The expression of Arg-1 in tumor tissues of mice was detected by immunochemistry analysis. As shown in Figure 12C, DPP markedly lowered the expression of Arg-1 (brown).…”

Section: ■ Introductionmentioning

confidence: 99%

Platinum(IV) Complexes as Inhibitors of STAT3 and Regulators of the Tumor Microenvironment To Control Breast Cancer

Cai,

Wang,

Chen

et al. 2023

J. Med. Chem.

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“…The microenvironment of lung cancer becomes immunosuppressive due to the regulation of the immune response activated by malignant cells, which aids tumor cells in escaping from immune surveillance [ 40 , 41 ]. Due to genetic instability, constant tumor cell division changes their phenotypes toward a poor immunogenicity that can avoid immune attack [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming

Huang

et al. 2022

Biology

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Lung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing potential agents against LUAD. This study explored the dysregulation of translation initiation factors, specifically eukaryotic initiation factors 4A1 (EIF4A1) and EIF4A2, in developing LUAD, as well as their underlying mechanisms. We found that the expression of EIF4A1, but not EIF4A2, was higher in tumor tissue and associated with poor clinical outcomes in LUAD patients. Elevated expression of EIF4H with poor prognosis may potentiate the oncogenic role of EIF4A1. Functional enrichment analysis revealed that upregulation of EIF4A1 was related to cell cycle regulation and DNA repair. The oncogenic effect of EIF4A1 was further elucidated by Gene Set Variation Analysis (GSVA). The GSVA score of the gene set positively correlated with EIF4A1 was higher in tumors and significantly associated with worse survival. In the meantime, gene set enrichment analysis (GSEA) also indicated that elevated EIF4A1 expression in LUAD patients was associated with a decreased infiltration score for immune cells by reducing anticancer immune cell types and recruiting immunosuppressive cells. Consistent with the results, the GSVA score of genes whose expression was negatively correlated with EIF4A1 was lower in the tumor tissue of LUAD cases with worse clinical outcomes and was strongly associated with the disequilibrium of anti-cancer immunity by recruiting anticancer immune cells. Based on the results from the present study, we hypothesize that the dysregulation of EIF4A1 might be involved in the pathophysiology of LUAD development by promoting cancer growth and changing the tumor immune microenvironment. This can be used to develop potential diagnostic biomarkers or therapeutic targets for LUAD.

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“…They are essential cellular components mediating immunosuppression. Substantial evidence has revealed MDSCs are closely linked with cancer stemness maintenance (67,68). In esophageal squamous cell carcinoma (ESCC), MDSCs can activate NEDD9 to enhance cancer stemness with the involvement of Notch signaling (69).…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

Current understanding of cancer stem cells: Immune evasion and targeted immunotherapy in gastrointestinal malignancies

Liu

2023

Front. Oncol.

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As a relatively rare population of cancer cells existing in the tumor microenvironment, cancer stem cells (CSCs) possess properties of immune privilege to evade the attack of immune system, regulated by the microenvironment of CSCs, the so-called CSCs niche. The bidirectional interaction of CSCs with tumor microenvironment (TME) components favors an immunosuppressive shelter for CSCs’ survival and maintenance. Gastrointestinal cancer stem cells (GCSCs) are broadly regarded to be intimately involved in tumor initiation, progression, metastasis and recurrence, with elevated tumor resistance to conventional therapies, which pose a major hindrance to the clinical efficacy for treated patients with gastrointestinal malignancies. Thus, a multitude of efforts have been made to combat and eradicate GCSCs within the tumor mass. Among diverse methods of targeting CSCs in gastrointestinal malignancies, immunotherapy represents a promising strategy. And the better understanding of GCSCs immunomodulation and immunoresistance mechanisms is beneficial to guide and design novel GCSCs-specific immunotherapies with enhanced immune response and clinical efficacy. In this review, we have gathered available and updated information to present an overview of the immunoevasion features harbored by cancer stem cells, and we focus on the description of immune escape strategies utilized by CSCs and microenvironmental regulations underlying CSCs immuno-suppression in the context of gastrointestinal malignancies. Importantly, this review offers deep insights into recent advances of CSC-targeting immunotherapeutic approaches in gastrointestinal cancers.

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MDSCs might be “Achilles heel” for eradicating CSCs

Cited by 9 publications

References 109 publications

Platinum(IV) Complexes as Inhibitors of STAT3 and Regulators of the Tumor Microenvironment To Control Breast Cancer

Platinum(IV) Complexes as Inhibitors of STAT3 and Regulators of the Tumor Microenvironment To Control Breast Cancer

Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming

Current understanding of cancer stem cells: Immune evasion and targeted immunotherapy in gastrointestinal malignancies

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