MiR-29c downregulates tumor-expressed B7-H3 to mediate the antitumor NK-cell functions in ovarian cancer

Deng, Mengqi; Wu, Di; Zhang, Yanqin; Jin, Zhaoyu; Miao, Jinwei

doi:10.1016/j.ygyno.2021.04.013

Cited by 22 publications

(19 citation statements)

References 42 publications

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“…The IC molecules, such as PD-1, CTLA-4 and CD276, inhibit the cytotoxic activity and promote the exhaustion of NK cells and T cells ( 26 , 27 ). RNA-seq results of NALM-6 cells showed that, compared with the control, miR-582 overexpression significantly upregulated the mRNA expression of CD276, which is an important IC molecule inhibiting NK-mediated cytotoxicity ( 26 ) ( Figure 6A ) . Then, three BCP-ALL cell lines were infected with pre-miR-582 and control lentivirus for 72 h, and the expression of CD276 was examined.…”

Section: Resultsmentioning

confidence: 99%

“…NK cells are important innate immune cells and have the ability to directly kill tumor cells without prior sensitization ( 25 ). Previous researches have shown that, in the TME, low expression of miR-29c and miR-142-5p upregulates the expression of some IC molecules such as CD276 and PD-L1, which further suppress the cytotoxic activity of NK cells and CD8 + T cells ( 26 , 27 ). In diffuse large B cell lymphoma (DLBCL), overexpression of miR-5590-3p upregulates PD-L1 expression, and the high expression of PD-L1 on DLBCL cells promotes immune escape by inhibiting the cytotoxic activity of CD8 + T cells ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

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miR-582 Suppresses the Proliferation of B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Cells and Protects Them From Natural Killer Cell-Mediated Cytotoxicity

Zhang

et al. 2022

Front. Immunol.

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B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignancy characterized by the aberrant accumulation of immature B-cell precursors in bone marrow and other lymphoid organs. Although several intrinsic regulatory signals participating in BCP-ALL have been clarified, detailed intrinsic and extrinsic mechanisms that regulate BCP-ALL progression have not been fully understood. In the current study, we report that miR-582 is downregulated in BCP-ALL cells compared with normal B cells. Forced overexpression of miR-582 attenuated BCP-ALL cell proliferation and survival. We found that miR-582 overexpression disturbed the mitochondrial metabolism of BCP-ALL cells, leading to less ATP but more ROS production. Mechanistically, we identified PPTC7 as a direct target of miR-582. MiR-582 overexpression inhibited the activity of CoQ10, which is downstream of PPTC7 and played an important positive regulatory role in mitochondrial electron transportation. Finally, we found that overexpression of miR-582 upregulated the expression of immune checkpoint molecule CD276 and reduced NK cell-mediated cytotoxicity against BCP-ALL cells. CD276 blockade significantly increased NK cell-mediated cytotoxicity against miR-582-overexpressing BCP-ALL cells. Together, our research demonstrates that miR-582 acts as a negative regulator of BCP-ALL cells by reducing proliferation and survival, but protects BCP-ALL cells from NK cell-mediated cytotoxicity, suggesting that miR-582 may be a new therapeutic biomarker for BCP-ALL with CD276 blocker.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-582 Suppresses the Proliferation of B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Cells and Protects Them From Natural Killer Cell-Mediated Cytotoxicity

Zhang

et al. 2022

Front. Immunol.

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“…B7-H3, an ideal target for cancer immunotherapy, has been widely explored. It was reported that miR-29c overexpression remarkably reduced B7-H3 in ovarian and breast cancer ( 48 , 49 ). The anti-B7-H3 antibody 8H9 (omburtamab) has shown clinical potential in treating central nervous system malignancies and non-small cell lung cancer, which promoted Fc-dependent NK cells through antibody-dependent cell-mediated cytotoxicity (ADCC) function ( 50 , 51 ).…”

Section: Discussionmentioning

confidence: 99%

Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer

Han

et al. 2022

Front. Immunol.

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BackgroundGallbladder cancer (GBC) is a mortal malignancy with limited therapeutic strategies. We aimed to develop novel immune scoring systems focusing on B7-H3, B7-H4, and HHLA2. We further investigated their potential clinical effects in predicting survival and immunotherapeutic efficacy for GBC.MethodsThis was a retrospective cohort study in a single center that explored the expression characteristics of B7-H3, B7-H4, and HHLA2. The immune scoring nomograms for prognostic were developed via logistic regression analyses. Their performance was evaluated using the Harrell concordance index (C-index) and decision curves analysis (DCA), and validated with calibration curves.ResultsB7-H3, B7-H4, and HHLA2 manifested with a relatively high rate of co-expression patterns in GBC tissues. They were associated with worse clinicopathological stage, suppression of immune microenvironment, and unfavorable prognosis in postoperative survival. B7 stratification established based on B7-H3, B7-H4, and HHLA2 was an independent prognostic predictor (p<0.05 in both groups). Moreover, immune stratification was also successfully constructed based on B7 stratification and the density of CD8+ TILs (all p<0.001). The prediction models were developed based on B7-/or immune stratification combined with the TNM/or Nevin staging system. These novel models have excellent discrimination ability in predicting survival and immunotherapeutic efficacy for GBC patients by DCA and clinical impact plots. Finally, dynamic nomograms were developed for the most promising clinical prediction models (B7-TNM model and Immune-TNM model) to facilitate prediction.ConclusionsImmune scoring systems focusing on B7-H3, B7-H4, and HHLA2 may effectively stratify the prognosis of GBC. Prognostic nomograms based on novel immune scoring systems may potentially predict survival and immunotherapeutic efficacy in GBC. Further valid verification is necessary.

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“…The inhibitory receptors expressed on NK cells include KIR, leukocyte immunoglobulin-like receptor (LILR), killer lectin-like receptor (KLR) (173), inhibitory receptor composed of NKG2A and CD94, B7H3 protein receptor, sialic acid-binding immunoglobulin-like lectin (Siglecs), TIM-3, LAG-3, TIGIT, CD-47, etc. (199)(200)(201)(202)(203)(204)(205)(206)(207). Blocking these inhibitory receptors can restore the activity of NK cells.…”

Section: The Treatment Strategies Based On Nk Cells For Gc Include Nk...mentioning

confidence: 99%

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

et al. 2022

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Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte–associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell–based therapeutic methods will be developed and applied.

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MiR-29c downregulates tumor-expressed B7-H3 to mediate the antitumor NK-cell functions in ovarian cancer

Cited by 22 publications

References 42 publications

miR-582 Suppresses the Proliferation of B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Cells and Protects Them From Natural Killer Cell-Mediated Cytotoxicity

miR-582 Suppresses the Proliferation of B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Cells and Protects Them From Natural Killer Cell-Mediated Cytotoxicity

Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

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