Lactate dehydrogenase B regulates macrophage metabolism in the tumor microenvironment

Frank, Ann-Christin; Raue, Rebecca; Fuhrmann, Dominik C.; Sirait‐Fischer, Evelyn; Reuse, Carsten; Weigert, Andreas; Lütjohann, Dieter; Hiller, Karsten; Syed, Shahzad N.; Brüne, Bernhard

doi:10.7150/thno.58380

Cited by 35 publications

(26 citation statements)

References 88 publications

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“…The crosstalk between tumor cells and macrophages is affected by microRNAs (miRNAs). Tumor-derived factor miRNAs, a kind of small non-coding RNA, can regulate target gene expression after transcription [ 122 ] ( Figure 4 A). According to reports, miRNA dysregulation can induce the occurrence of a variety of malignant tumors, and it has a significant impact on tumor immune escape, invasion, angiogenesis, migration and drug resistance [ 123 , 124 ].…”

Section: Macrophages In Tumor Therapymentioning

confidence: 99%

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

Júnior

Cruz

et al. 2021

Pharmaceutics

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The tumor microenvironment (TME) plays a central role in regulating antitumor immune responses. As an important part of the TME, alternatively activated type 2 (M2) macrophages drive the development of primary and secondary tumors by promoting tumor cell proliferation, tumor angiogenesis, extracellular matrix remodeling and overall immunosuppression. Immunotherapy approaches targeting tumor-associated macrophages (TAMs) in order to reduce the immunosuppressive state in the TME have received great attention. Although these methods hold great potential for the treatment of several cancers, they also face some limitations, such as the fast degradation rate of drugs and drug-induced cytotoxicity of organs and tissues. Nanomedicine formulations that prevent TAM signaling and recruitment to the TME or deplete M2 TAMs to reduce tumor growth and metastasis represent encouraging novel strategies in cancer therapy. They allow the specific delivery of antitumor drugs to the tumor area, thereby reducing side effects associated with systemic application. In this review, we give an overview of TAM biology and the current state of nanomedicines that target M2 macrophages in the course of cancer immunotherapy, with a specific focus on nanoparticles (NPs). We summarize how different types of NPs target M2 TAMs, and how the physicochemical properties of NPs (size, shape, charge and targeting ligands) influence NP uptake by TAMs in vitro and in vivo in the TME. Furthermore, we provide a comparative analysis of passive and active NP-based TAM-targeting strategies and discuss their therapeutic potential.

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Section: Macrophages In Tumor Therapymentioning

confidence: 99%

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

Júnior

Cruz

et al. 2021

Pharmaceutics

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“…and Frank et al. have also found that LDH can recruit and regulate tumor-associated macrophage metabolism in breast cancer to affect breast cancer cell proliferation and invasion ( 20 , 35 ). Ruiz-Rodado et al.…”

Section: Discussionmentioning

confidence: 99%

“…Under the condition of excessive metabolism of tumor cells, LDH promotes the tumor-specific Warburg effect; this produces energy and lactic acid through glycolysis, which is involved in the tricarboxylic acid cycle after being re-ingested by cancer cells (34). Wang et al and Frank et al have also found that LDH can recruit and regulate tumor-associated macrophage metabolism in breast cancer to affect breast cancer cell proliferation and invasion (20,35). Ruiz-Rodado et al demonstrated that the glioma IDH1-mut invasive cell line obtained a high glycolysis phenotype through the specific deletion of methylation of the LDH promoter, which was associated with a worse survival rate (36).…”

Section: An Increasing Number Of Studies Have Indicated That Tumorigenesis Is Closely Associated With Abnormalities In Thementioning

confidence: 99%

A Clinical Prognostic Model Based on Preoperative Hematological and Clinical Parameters Predicts the Progression of Primary WHO Grade II Meningioma

et al. 2021

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PurposeThe purpose was to explore the correlation between hematological parameters and the progression of WHO grade II meningioma, and establish a clinical prognostic model based on hematological parameters and clinical prognostic factors to predict the progression-free survival (PFS) of patients.MethodsA total of 274 patients with WHO grade II meningiomas were included. Patients were randomly divided into a training cohort (192, 70%) and a test cohort (82, 30%). In the training cohort, the least absolute shrinkage and selection operator Cox regression analysis were used to screen for hematological parameters with prognostic value, and the hematological risk model (HRM) was constructed based on these parameters; univariate and multivariate Cox regression analyses were utilized to screen for clinical prognostic factors, and a clinical prognostic model was constructed based on clinical prognostic factors and HRM. The prognostic stability and accuracy of the HRM and clinical prognostic model were verified in the test cohort. Subgroup analysis was performed according to the patients’ different clinical characteristics.ResultsPreoperative neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, albumin-to-globulin ratio, D-dimer, fibrinogen, and lactate dehydrogenase were associated with the PFS of patients. The areas under curve of the HRM were 0.773 (95% confidence interval [CI] 0.707–0.839) and 0.745 (95% CI 0.637–0.852) in the training cohort and test cohort, respectively. The progression risk was higher in the high-risk group than that in the low-risk group categorized by the optimal cutoff value (2.05) of hematological risk scores. The HRM, age, tumor location, tumor size, peritumoral edema, extent of resection, Ki-67 index, and postoperative radiotherapy were the prognostic factors for the progression of meningiomas. The corrected C-index of the clinical prognosis model was 0.79 in the training cohort. Clinical decision analysis showed that the clinical prognostic model could be used to obtain favorable clinical benefits. In the subgroup analysis, the HRM displayed excellent prognostic stability and general applicability in different subgroups.ConclusionsPreoperative hematological parameters are associated with the postoperative progression of WHO grade II meningiomas. The clinical prognosis model constructed based on hematological parameters and clinical prognostic factors has favorable predictive accuracy and clinical benefits.

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“…Lactate dehydrogenase B (LDHB) is a glycolysis-related enzyme that catalyzes the interconversion of pyruvate and lactate, whose function in macrophages has been poorly investigated [59]. Frank et al demonstrated that miR-375 derived from breast cancer cells is captured by TAMs, where it reduces LDHB expression levels, likely by directly targeting its transcript.…”

Section: Non-coding Rnas In the Regulation Of Bc Cells And Tam Metabo...mentioning

confidence: 99%

“…The increased production of lactate and sterol by TAMs in the TME boosts tumor progression by stimulating cancer cell proliferation and survival. Therefore, miR-375 can be a promising target to selectively interfere with TAM tumor-promoting functions by reverting their metabolic status [59].…”

Section: Non-coding Rnas In the Regulation Of Bc Cells And Tam Metabo...mentioning

confidence: 99%

Non-Coding RNAs in the Crosstalk between Breast Cancer Cells and Tumor-Associated Macrophages

Benedetti

Turco

Fontemaggi

et al. 2022

ncRNA

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Non-coding RNAs (ncRNAs) play a pivotal role in regulating the tumor microenvironment (TME) by controlling gene expression at multiple levels. In tumors, ncRNAs can mediate the crosstalk between cancer cells and other cells in the TME, such as immune cells, stromal cells, and endothelial cells, influencing tumor development and progression. Tumor-associated macrophages (TAMs) are among the most abundant inflammatory cells infiltrating solid cancers that promote tumorigenesis, and their infiltration correlates with a poor prognosis in many tumors. Cancer cells produce different ncRNAs that orchestrate TAM recruitment and polarization toward a tumor-promoting phenotype. Tumor-reprogrammed macrophages shape the TME by promoting angiogenesis and tissue remodeling, and suppressing the anti-tumor activity of adaptive immune cells. TAMs can also produce ncRNA molecules that boost cancer cell proliferation and direct their phenotype and metabolic changes facilitating cancer progression and metastasis. This review will focus on the crosstalk between cancer cells and TAMs mediated by microRNAs and long non-coding RNAs during breast cancer (BC) initiation and progression.

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Lactate dehydrogenase B regulates macrophage metabolism in the tumor microenvironment

Cited by 35 publications

References 88 publications

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

A Clinical Prognostic Model Based on Preoperative Hematological and Clinical Parameters Predicts the Progression of Primary WHO Grade II Meningioma

Non-Coding RNAs in the Crosstalk between Breast Cancer Cells and Tumor-Associated Macrophages

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