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Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid cells with immunosuppressive effects, which undergo massive expansion during tumor progression. These cells not only support immune escape directly but also promote tumor invasion via various non-immunological activities. Besides, this group of cells are proved to impair the efficiency of current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs are considered as potential therapeutic targets for cancer therapy. Treatment strategies targeting MDSCs have shown promising outcomes in both preclinical studies and clinical trials when administrated alone, or in combination with other anticancer therapies. In this review, we shed new light on recent advances in the biological characteristics and immunosuppressive functions of MDSCs. We also hope to propose an overview of current MDSCs-targeting therapies so as to provide new ideas for cancer treatment.

SUBMITTER: Li K

PROVIDER: S-EPMC8497485 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.

Li Kai K Shi Houhui H Zhang Benxia B Ou Xuejin X Ma Qizhi Q Chen Yue Y Shu Pei P Li Dan D Wang Yongsheng Y

Signal transduction and targeted therapy 20211007 1

Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid cells with immunosuppressive effects, which undergo massive expansion during tumor progression. These cells not only support immune escape directly but also promote tumor invasion via various non-immunological activities. Besides, this group of cells are proved to impair the efficiency of current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs are considered as p ...[more]

PMID: 34620838

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Project description:BackgroundMyeloid-derived suppressor cells (MDSCs) are potent suppressors of immune function and may play a key role in the development and progression of metastatic cancers. Aerobic exercise has been shown to have anticancer effects, yet the mechanisms behind this protection are largely unknown. Therefore, we examined the effects of physical activity on MDSC accumulation and function.MethodsFemale BALB/c mice were assigned to one of two primary groups: sedentary tumor (SED+TUM) or wheel run tumor (WR+TUM). After 6 weeks of voluntary wheel running, all animals were randomly subdivided into 4 different timepoint groups; 16, 20, 24, and 28 days post-tumor injection. All mice were inoculated with 4T1 mammary carcinoma cells in the mammary fat pad and WR groups continued to run for the specified time post-injection. Spleen, blood, and tumor samples were analyzed using flow cytometry to assess proportions of MDSCs.ResultsCells expressing MDSC biomarkers were detected in the spleen, blood, and tumor beginning at d16. However, since there was no evidence of immunosuppressive function until d28, we refer to them as immature myeloid cells (IMCs). Compared to SED+TUM, levels of IMCs in the spleen were significantly lower (p < 0.05) in WR+TUM at day 16 (33.0 ± 5.2%; 23.1 ± 10.2% of total cells, respectively) and day 20 (33.9 ± 8.1%; 24.3 ± 5.1% of total cells, respectively). Additionally, there were fewer circulating IMCs in WR+TUM at day 16 and MDSC levels were significantly lower (p < 0.05) in the tumor at day 28 in WR+TUM. Additionally, a non-significant 62% and 26% reduction in metastatic lung nodules was observed at days 24 and 28, respectively. At day 28, MDSCs harvested from SED+TUM significantly suppressed CD3+CD4+ T cell proliferation (3.2 ± 1.3 proliferation index) while proliferation in WR+TUM MDSC co-cultures (5.1 ± 1.7 proliferation index) was not different from controls.ConclusionsThese findings suggest that physical activity may delay the accumulation of immunosuppressive MDSCs providing a broader window of opportunity for interventions with immunotherapies.

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Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.

Publications

Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.

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