A5091343254- Autophagy in Disease and Therapy
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Cancer Immunotherapy and Biomarkers
- Adenosine and Purinergic Signaling
- CAR-T cell therapy research
- Extracellular vesicles in disease
- Cell Adhesion Molecules Research
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Chemokine receptors and signaling
- Cellular Mechanics and Interactions
- Chronic Lymphocytic Leukemia Research
- Nanoplatforms for cancer theranostics
- Protein Degradation and Inhibitors
- Nanoparticle-Based Drug Delivery
- Cancer-related molecular mechanisms research
- interferon and immune responses
Luxembourg Institute of Health
2015-2024
Weatherford College
2022
University of Luxembourg
2021
Laboratoire National de Santé
2005-2015
Inserm
2011-2015
Centre Hospitalier de Luxembourg
2010-2015
Institut Gustave Roussy
2013-2015
Institut de Biologie et de Chimie des Protéines
2002-2015
Université Claude Bernard Lyon 1
2012-2015
Assistance Publique – Hôpitaux de Paris
2013
Tumor-infiltrating myeloid cells such as myeloid-derived suppressor (MDSCs) and tumor-associated macrophages (TAMs) form an important component of the hypoxic tumor microenvironment. Here, we investigated influence hypoxia on immune checkpoint receptors (programmed death [PD]-1 CTLA-4) their respective ligands (PD-1 ligand 1 [PD-L1], PD-L2, CD80, CD86) MDSCs. We demonstrate that MDSCs at site show a differential expression PD-L1 compared with from peripheral lymphoid organ (spleen). Hypoxia...
Significance Natural killer (NK) cells are effectors of the antitumor immunity, able to kill cancer through release cytotoxic protease granzyme B. NK-based therapies have recently emerged as promising anticancer strategies. It is well established that hypoxic microenvironment interferes with function immune and constitutes a major obstacle for immunotherapies. We showed breast evade effective NK-mediated killing under hypoxia by activating autophagy we identified be responsible degradation...
Tumor-derived microvesicles (TD-MVs) are key mediators which shed by cancer cells and can sensitize neighboring in the tumor microenvironment. TD-MVs extracellular vesicles composed of exosomes MVs promote invasion metastasis. Intratumoral hypoxia is an integral component all solid tumors. The relationship between hypoxic tumor-shed NK-mediated cytotoxicity remains unknown. In this paper, we reported that derived from qualitatively differ those normoxic cells. Using multiple models, showed...
Epithelial-to-mesenchymal transition (EMT) mediates cancer cell invasion, metastasis, and drug resistance, but its impact on immune surveillance has not been explored. In this study, we investigated the functional consequences of mode epithelial plasticity targeted lysis by cytotoxic T lymphocytes (CTL). Acquisition EMT phenotype in various derivatives MCF-7 human breast cells was associated with dramatic morphologic changes actin cytoskeleton remodeling, CD24(-)/CD44(+)/ALDH(+) stem...
Abstract The relationship between hypoxic stress, autophagy, and specific cell-mediated cytotoxicity remains unknown. This study shows that hypoxia-induced resistance of lung tumor to cytolytic T lymphocyte (CTL)–mediated lysis is associated with autophagy induction in target cells. In turn, this correlates STAT3 phosphorylation on tyrosine 705 residue (pSTAT3) HIF-1α accumulation. Inhibition by siRNA targeting either beclin1 or Atg5 resulted impairment pSTAT3 restoration cell susceptibility...
PD-L1 expression and regulation by mesenchymal tumor cells remain largely undefined. Here, we report that among different EMT-activated MCF7 human breast cancer cell clones, was differentially upregulated in sh-WISP2, MCF7–1001/2101, MDA-MB-231 but not SNAI1 SNAI1–6SA cells. Mechanistic investigations revealed siRNA silencing of ZEB-1, SNAI1, TWIST, or SLUG overexpression miR200 family members sh-WISP2 strongly decreased expression. Thus, propose depends on the EMT-TF involved EMT...
One of the major challenges limiting efficacy anti-PD-1/PD-L1 therapy in nonresponding patients is failure T cells to penetrate tumor microenvironment. We showed that genetic or pharmacological inhibition Vps34 kinase activity using SB02024 SAR405 (Vps34i) decreased growth and improved mice survival multiple models by inducing an infiltration NK, CD8+, CD4+ effector melanoma CRC tumors. Such resulted establishment a cell-inflamed microenvironment, characterized up-regulation pro-inflammatory...
Significance The failure in achieving a durable clinical immune response against cancer cells depends on the ability of to establish microenvironment that prevent cytotoxic infiltrate tumors and kill cells. Therefore, key approach successful antitumor is harness strategies allowing reorientation tumor. Herein we reveal inhibiting autophagy induces massive infiltration natural killer into tumor bed, subsequent dramatic decrease volume melanomas. These results highlight role targeting breaking...
In solid tumors, cancer stem cells (CSCs) or tumor-initiating (TICs) are often found in hypoxic niches. Nevertheless, the influence of hypoxia on TICs is poorly understood. Using previously established, TIC-enrichedpatient-derived colorectal (CRC) cultures, we show that increases self-renewal capacity while inducing proliferation arrest their more differentiated counterpart cultures. Gene expression data revealed macroautophagy/autophagy as one major pathways induced by TICs. Interestingly,...
Abstract Hypoxia in the tumor microenvironment plays a central role evolution of immune escape mechanisms by cells. In this study, we report definition miR-210 as miRNA regulated hypoxia lung cancer and melanoma, documenting its involvement blunting susceptibility cells to lysis antigen-specific cytotoxic T lymphocytes (CTL). was induced hypoxic zones human tissues. Its attenuation significantly restored autologous CTL-mediated lysis, independent cell recognition CTL reactivity. A...
Myeloid-derived suppressor cells (MDSC) contribute significantly to the malignant characters conferred by hypoxic tumor microenvironments. However, selective biomarkers of MDSC function in this critical setting have not been defined. Here, we report that miR-210 expression is elevated hypoxia-inducible factor-1α (HIF1α) localized tumors, compared with splenic from tumor-bearing mice. In MDSC, determined HIF1α was bound directly a transcriptionally active hypoxia-response element proximal...
Elucidation of the underlying molecular mechanisms immune evasion in cancer is critical for development immunotherapies aimed to restore and stimulate effective antitumor immunity. Here, we evaluate role actin cytoskeleton breast cell resistance cytotoxic natural killer (NK) cells. A significant fraction cells responded NK-cell attack via a surprisingly rapid massive accumulation F-actin near immunologic synapse, process termed "actin response." Live-cell imaging provided direct evidence...
Human natural killer (NK) cells can be subdivided in several subpopulations on the basis of relative expression adhesion molecule CD56 and activating receptor CD16. Whereas blood CD56brightCD16dim/- NK are classically viewed as immature precursors cytokine producers, larger CD56dimCD16bright subset is considered most cytotoxic one. In peripheral healthy donors, we noticed existence a population CD56dimCD16dim that was frequently higher number than CD56bright subsets even expanded occasional...
Abstract Clear cell renal carcinomas (RCC) frequently display inactivation of von Hippel-Lindau (VHL) gene leading to increased level hypoxia-inducible factors (HIF). In this study, we investigated the potential role HIF2α in regulating RCC susceptibility natural killer (NK) cell–mediated killing. We demonstrated that line 786-0 with mutated VHL was resistant NK-mediated lysis as compared VHL-corrected (WT7). This resistance found require stabilization. On basis global expression profiling...
Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia activates pathways. The aim of this study was determine the role hypoxia-induced autophagy GBM.Pharmacological inhibition applied combination bevacizumab patient-derived xenografts (PDXs). Sensitivity towards inhibitors tested vitro under normoxia hypoxia, followed by transcriptomic analysis. Genetic interference done using...
Abstract Hypoxia is a key factor responsible for the failure of therapeutic response in most solid tumors and promotes acquisition tumor resistance to various antitumor immune effectors. Reshaping hypoxic suppressive microenvironment improve cancer immunotherapy still relevant challenge. We investigated impact inhibiting HIF-1α transcriptional activity on cytotoxic cell infiltration into B16-F10 melanoma. showed that expressing deleted form displayed increased levels NK CD8 + effector T...
While the autophagic process is mainly regulated at post-translational level, a growing body of evidence suggests that autophagy might also be transcriptional level. The identification transcription factors involved in regulation genes has provided compelling for such regulation. In this context, powerful high throughput analysis tool to simultaneously monitor expression level urgently needed. Here we describe setting up first comprehensive human database (HADb, available www.autophagy.lu)...