Biology subjects

Bordas, M.

Publications and source records attributed to Bordas, M..

3 recordsLinked to original sources

bioRxiv2022

Lipid Droplets Fuel Small Extracellular Vesicle Biogenesis

Despite an increasing gain of knowledge regarding small extracellular vesicle (sEV) composition and functions in cell-cell communication, the mechanism behind their biogenesis remains unclear. Here, we revealed for the first time that the sEV biogenesis and release into the microenvironment are tightly connected with another important organelle: Lipid Droplets (LD). We have observed this correlation using different human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results showed that the use of external stimuli such as radiation, pH, hypoxia, or lipid interfering drugs, known to affect the LD content, had a similar effect in terms of sEV secretion. Additional validations were brought using multiple omics data, at the mRNA and protein levels. Altogether, the possibility to fine-tune sEV biogenesis by targeting LDs, could have a massive impact on the amount, the cargos and the properties of those sEVs, paving the way for new clinical perspectives. Significance Statement

cancer biology↗

bioRxiv2020

EOMES and IL-10 regulate anti-tumor activity of PD-1+ CD4+ T-cells in B-cell Non-Hodgkin lymphoma

The transcription factor Eomesodermin (EOMES) promotes IL-10 production of CD4+ T-cells, which has been linked to immunosuppressive and cytotoxic activities. We detected EOMES-expressing CD4+ T-cells in lymph node samples of patients with chronic lymphocytic leukemia (CLL) or diffuse large B-cell lymphoma. This was in line with an observed expansion of EOMES-positive CD4+ T-cells in leukemic E{micro}-TCL1 mice, a well-established model of CLL, and upon adoptive transfer of TCL1 leukemia in mice. Transcriptome and flow cytometry analyses revealed that EOMES does not only drive the transcription of IL-10, but rather controls a unique differentiation program in CD4+ T-cells. Moreover, EOMES was necessary for the accumulation of a specific CD4+ T-cell subset that expresses IFN{gamma} and IL-10, as well as inhibitory receptors, like PD-1 and LAG3. T-cell transfer studies in leukopenic Rag2-/- mice showed that EOMES-deficient CD4+ T-cells were inferior in controlling TCL1 leukemia development compared to wildtype T-cells, even though expansion of Eomes-/- CD4+ T-cells was observed. We further showed that control of TCL1 leukemia was driven by IL-10 receptor-mediated signals, as Il10rb-deficient CD4+ T-cells showed impaired anti-leukemia activity. Altogether, our data suggest that IL-10 producing PD-1+ CD4+ T-cells contribute to CLL control in an EOMES- and IL-10R-dependent manner.

cancer biology↗

bioRxiv2019

Dissecting intratumor heterogeneity of nodal B cell lymphomas on the transcriptional, genetic, and drug response level

Tumor heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is well-known to affect the efficacy of anti-cancer drugs, most personalized treatment approaches do not account for intratumor heterogeneity. We addressed this issue by studying the heterogeneity of lymph node-derived B cell non-Hodgkin lymphoma (B-NHL) by single cell RNA-sequencing (scRNA-seq) and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subclones and compared their drug response and genomic profiles. Malignant subclones of the same patient responded strikingly different to anti-cancer drugs ex vivo, which recapitulated subclone-specific drug sensitivity during in vivo treatment. Tumor infiltrating T cells represented the majority of non-malignant cells, whose gene expression signatures were similar across all donors, whereas the frequencies of T cell subsets varied significantly between the donors. Our data provide new insights into the heterogeneity of B-NHL and highlight the relevance of intratumor heterogeneity for personalized cancer therapies.

cancer biology↗