Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy

Li, Xueyan; Zhong, Jiahui; Deng, Xian-Yu; Guo, Xuan; Lu, Yantong; Lin, Jingxia; Huang, Xuhui; Wang, Changjun

doi:10.3389/fimmu.2021.754196

Cited by 33 publications

(20 citation statements)

References 134 publications

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“…Reprogramming or reducing MDSCs can help reactivate the immune system's antitumor response. 113 Recently, an interesting nanoplatform was developed by Zhou et al to enhance pyroptosis-based immunotherapy and overcome immune escape mediated by MDSCs. 114 Pyroptosis, programmed cell death, can increase the immune response of tumor cells.…”

Section: Nanotechnological Targeting Strategies To Modulate Tme Of Pdacmentioning

confidence: 99%

Advancing Cancer Treatment Through Nanotechnology Driven Immunotherapy for Pancreatic Cancer

Kamalasanan,

et al. 2023

ACS Appl. Nano Mater.

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Pancreatic cancer is expected to be the most lethal cancer by 2030; among that, PDAC is the most prominent one, which is immune resistant, posing substantial hurdles to creating effective therapeutics. Despite the advancements in immunotherapy, its application in PDAC is less successful. Uniquely, PDAC tumors are “cold” to immune response mainly due to suppression of spatiotemporal immune signatures from cells and tumor microenvironment. Contrary to other immune-responsive tumors, immunotherapy in combination with chemotherapy in PDAC, is still diffusion-limiting to the drugs and less cytotoxic to cancer cells. Moreover, newer approaches exploring nanotechnology are being tried to make PDAC “hot” and immunogenic in nature and are promising. This review analyses the design strategies of nanosystems for effective spatiotemporal signaling to improve immune response to PDAC tumors. Particularly, that helps to overcome early evasion in phase I, and resistance to the antitumor immune response by modulating cellular and tumor microenvironment (TME) through the latest advancements in nanotechnology, immune mechanisms, and potential delivery routes for PDAC treatment. Ongoing and completed clinical trials of nanotechnology-driven immunotherapies in pancreatic cancer are also highlighted here. Overall, this approach of nanotechnological strategy to enhance immunotherapy in PDAC holds great promise and may contribute to a groundbreaking shift in the therapeutic management of PDAC and reduce the mortality rate of this lethal disease.

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Section: Nanotechnological Targeting Strategies To Modulate Tme Of Pdacmentioning

confidence: 99%

Advancing Cancer Treatment Through Nanotechnology Driven Immunotherapy for Pancreatic Cancer

Kamalasanan,

et al. 2023

ACS Appl. Nano Mater.

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“…Tregs secrete immunosuppressive cytokines which inhibit cytotoxic T cell function or limit the number of IL-2 that can activate cytotoxic T cells. 124 Similar to Tregs, MDSCs 125,126 and TAMs 127,128 were found to negatively modulate the function of T cells in the TME by modulating tumour vasculature or pre-metastatic niche formation, producing various anti-inflammatory cytokines, and inducing epithelial-mesenchymal transition (EMT) of tumour cells. [125][126][127][128] For instance, Cervantes et al demonstrated that the co-culture of CAR-T cells with MDSCs could reduce the T cell production of IFNγ and inhibit the CAR-T cell activation.…”

Section: Immunosuppressive Cells and Cytokines Inhibit The Function O...mentioning

confidence: 99%

Engineering chimeric antigen receptor T cells for solid tumour therapy

Liu

Cheng

et al. 2022

Clinical & Translational Med

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Cell‐based immunotherapy, for example, chimeric antigen receptor T (CAR‐T) cell immunotherapy, has revolutionized cancer treatment, particularly for blood cancers. However, factors such as insufficient T cell tracking, tumour heterogeneity, inhibitory tumour microenvironment (TME) and T cell exhaustion limit the broad application of CAR‐based immunotherapy for solid tumours. In particular, the TME is a complex and evolving entity, which is composed of cells of different types (e.g., cancer cells, immune cells and stromal cells), vasculature, soluble factors and extracellular matrix (ECM), with each component playing a critical role in CAR‐T immunotherapy. Thus, developing approaches to mitigate the inhibitory TME factors is critical for future success in applying CAR‐T cells for solid tumour treatment. Accordingly, understanding the bilateral interaction of CAR‐T cells with the TME is in pressing need to pave the way for more efficient therapeutics. In the following review, we will discuss TME‐associated aspects with an emphasis on T cell trafficking, ECM barriers, abnormal vasculature, solid tumour heterogenicity and immune suppressive microenvironment. We will then summarize current engineering strategies to overcome the challenges posed by the TME‐associated factors. Lastly, the future directions for engineering efficient CAR‐T cells for solid tumour therapy will be discussed.

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“…Studies indicate that regulatory T cells (Tregs) and other cell populations, namely, myeloid-derived suppressor cells (MDSCs; attracted to TME by low-grade chronic inflammatory signals) and tumor-associated macrophages (TAMs) ( 17 ), are mainly responsible for the immunosuppression observed in PC ( 18 ). Among them, MDSCs emerge as potential therapeutic targets ( 19 ).…”

Section: Prostate Cancer—epidemiologymentioning

confidence: 99%

Myeloid-Derived Suppressor Cells as Key Players and Promising Therapy Targets in Prostate Cancer

Siemińska

Baran

2022

Front. Oncol.

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Prostate cancer (PC) is the second most often diagnosed malignancy in men and one of the major causes of cancer death worldwide. Despite genetic predispositions, environmental factors, including a high-fat diet, obesity, a sedentary lifestyle, infections of the prostate, and exposure to chemicals or ionizing radiation, play a crucial role in PC development. Moreover, due to a lack of, or insufficient T-cell infiltration and its immunosuppressive microenvironment, PC is frequently classified as a “cold” tumor. This is related to the absence of tumor-associated antigens, the lack of T-cell activation and their homing into the tumor bed, and the presence of immunological cells with regulatory functions, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg), and tumor-associated macrophages (TAMs). All of them, by a variety of means, hamper anti-tumor immune response in the tumor microenvironment (TME), stimulating tumor growth and the formation of metastases. Therefore, they emerge as potential anti-cancer therapy targets. This article is focused on the function and role of MDSCs in the initiation and progression of PC. Clinical trials directly targeting this cell population or affecting its biological functions, thus limiting its pro-tumorigenic activity, are also presented.

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Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy

Cited by 33 publications

References 134 publications

Advancing Cancer Treatment Through Nanotechnology Driven Immunotherapy for Pancreatic Cancer

Advancing Cancer Treatment Through Nanotechnology Driven Immunotherapy for Pancreatic Cancer

Engineering chimeric antigen receptor T cells for solid tumour therapy

Myeloid-Derived Suppressor Cells as Key Players and Promising Therapy Targets in Prostate Cancer

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