Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs

Boibessot, Clovis; Joncas, France‐Hélène; Park, Aerin; Berrehail, Zohra; Pelletier, Jean‐François; Gris, Typhaine; Bergeron, Alain; Toren, Paul

doi:10.1038/s41598-021-98903-y

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…As previously observed, a comparison of immune cell marker expression (CD45, MHC-II, CD206) within viable cells by flow cytometry between immediately processed tumour tissues and those cultured for 72h did not show any significant difference ( Figure 6B ) ( 30 ). We next analysed the expression of the M1 and M2 markers within the macrophage population defined as CD45 + /CD11b + /F4/80 + Ly6G - cells.…”

Section: Resultssupporting

confidence: 73%

“…A complex and dynamic communication between the cancer cells and immune cells within the prostate TME greatly influences tumour survival and growth. Macrophages, one of the key immune cells present within the tumour and its periphery, contribute to tumour resistance and metastases ( 30 ). The advanced TRAMP TME is marked by an abundance of immunosuppressive M2 macrophages, PMN-MDSCs with decreased M1, and mature DCs.…”

Section: Discussionmentioning

confidence: 99%

“…Late TRAMP biopsies were cultured as previously described ( 30 ). Briefly, fresh tumour tissues were washed in Hanks’ Balanced Salt Solution (HBSS) (Gibco, USA), and then cut into ~1mm pieces.…”

Section: Methodsmentioning

confidence: 99%

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Immunomodulatory Role of Surfactant Protein-D in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model

et al. 2022

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Surfactant protein D (SP-D), a pattern recognition molecule, is emerging as a potent anti-tumoural innate immune defense molecule in a range of cancers. Previously, SP-D expression was found to be significantly downregulated at the malignant sites of human prostate adenocarcinoma and associated with an increasing Gleason score and severity. We recently reported selective induction of intrinsic apoptosis by a recombinant fragment of human SP-D (rfhSP-D) in the human Prostate cancer (PCa) biopsy explants and cells with glucose regulated protein of 78 (GRP78) as one of the key interacting partners. The present study evaluated the expression of SP-D in early and advanced stages of PCa using transgenic adenocarcinoma of mouse prostate (TRAMP) model. Both early and late stages of PCa showed significantly decreased SP-D mRNA expression and increased proteolytic degradation of SP-D protein. Systemic and tumoural immunophenotyping of TRAMP model revealed increased serine proteases producing granulocytes and polymorphonuclear myeloid-derived suppressor cells (PMN MDSCs) in the late stage; the serine proteases secreted by these cells could be involved in the degradation of SP-D. Susceptibility of rfhSP-D to elastase-mediated proteolysis provided the rationale to use an elastase-inhibitor to sustain intact rfhSP-D in the tumour microenvironment. The study revealed an immunomodulatory potential of rfhSP-D and elastase inhibitor, sivelestat, to induce macrophage polarization towards M1 with downregulation of PMN MDSCs in ex-vivo cultured TRAMP tumours. Furthermore, rfhSP-D induced immunogenic cell death in murine PCa cells and in TRAMP explants. The findings highlight that SP-D plays an anti-tumourigenic role in PCa by inducing immunogenic cell death and immunomodulation while the prostate tumour milieu adversely impacts SP-D by inhibiting its transcription, and enhancing its proteolytic degradation. Transformation of an immunologically “cold tumour” into a “hot tumour” implicates therapeutic potential of rfhSP-D in PCa.

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Section: Resultssupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory Role of Surfactant Protein-D in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model

et al. 2022

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“…M2 macrophages secreted chemokines such as CCL17 and CXCL13 ( Liu Y. et al, 2020 ; Xie et al, 2021 ). Meanwhile, CCL19 and CCL21 were shown to be associated with M1 macrophage chemotaxis ( Xuan et al, 2015 ; Boibessot et al, 2021 ). Chemokines such as CCL3 and CCL4 were upregulated in M1 macrophages compared to M2 macrophages ( Hörhold et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Tan

Liu

et al. 2022

Front. Pharmacol.

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Pancreatic adenocarcinoma (PAAD) is a malignant cancer with high incidence and mortality. Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of PAAD and contributes to tumorigenesis and progression through numerous mechanisms. This study aimed to identify a novel glycolysis-related lncRNA-miRNA-mRNA ceRNA signature in PAAD and explore its potential molecular function. We first calculated the glycolysis score for each PAAD patient by the ssGSEA algorithm and found that patients with higher hallmark glycolysis scores had poorer prognosis. Subsequently, we obtained a novel glycolysis-related LINC02432/hsa-miR-98–5p/HK2 axis from the TCGA and GEO databases using comprehensive bioinformatics analysis and developed a nomogram to predict overall survival. Furthermore, functional characterization analysis revealed that LINC02432/hsa-miR-98–5p/HK2 axis risk score was negatively correlated with ferroptosis. The tumor immune infiltration analysis suggested positive correlations between ceRNA risk score and infiltrated M0 macrophage levels in PAAD. Correlation analysis found that ceRNA risk scores were positively correlated with four chemokines (CXCL3, CXCL5, CXCL8 and CCL20) and one immune checkpoint gene (SIGLEC15). Meanwhile, tumor mutation burden (TMB), an indicator for predicting response to immunotherapy, was positively correlated with ceRNA risk score. Finally, the drug sensitivity analysis showed that the high-risk score patients might be more sensitive to EGFR, MEK and ERK inhibitors than low-risk score patients. In conclusion, our study suggested that LINC02432/hsa-miR-98–5p/HK2 axis may serve as a novel diagnostic, prognostic, and therapeutic target in PAAD treatment.

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“…The antiandrogen therapy, apalutamide, was shown to radiosensitize PDX-TS PCa demonstrating a possible therapeutic treatment for AR-dependent PCa ( 19 ). Explants are also useful for studying resident immune cells and PDEs were recently used to show an increase in CD163+/CD68+ macrophages after enzalutamide ( 23 ).…”

Section: Therapeutic Responses In Ex Vivo Pde and Tsmentioning

confidence: 99%

Harnessing the Utility of Ex Vivo Patient Prostate Tissue Slice Cultures

Perez

Nonn

2022

Front. Oncol.

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Patient-derived prostate tissue explant cultures are powerful research tools that offer the potential for personalized medicine. These cultures preserve the local microenvironment of the surrounding stroma but are not without limitations and challenges. There are several methods and processing techniques to culture tissue ex vivo, that include explant tissue chunks and precision-cut tissue slices. Precision-cut tissue slices provide a consistent distribution of nutrients and gases to the explant. Herein we summarize the prostate tissue slice method, its limitations and discuss the utility of this model, to investigate prostate biology and therapeutic treatment responses.

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Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs

Cited by 6 publications

References 32 publications

Immunomodulatory Role of Surfactant Protein-D in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model

Immunomodulatory Role of Surfactant Protein-D in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Harnessing the Utility of Ex Vivo Patient Prostate Tissue Slice Cultures

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