Project description:Tumor infiltrating neutrophils (TAN) have been shown to exert both pro- and anti-tumoral activities and their recruitment and polarization are triggered by tumor-derived signals. Resident mesenchymal stromal cells (MSC) could contribute to tumor-supportive cell niche and have been shown to display tumor-specific transcriptomic, phenotypic, and functional features compared to normal tissue. In our study, we investigate whether these two cell subsets establish a bidirectional crosstalk in the context of B-cell lymphoma. We used microarrays to explore how neutrophils could trigger the polarization of tumor-supportive stromal cells. Gene expression analysis were performed on stromal cells (MSC) derived from bone marrow (BM) or tonsil (Resto) of healthy donors. These BM-MSC (n=3) or Resto (n=3) were primed or not with neutrophils for 1 day to induce stromal modification.
Project description:Tumor infiltrating neutrophils (TAN) have been shown to exert both pro- and anti-tumoral activities and their recruitment and polarization are triggered by tumor-derived signals. Resident mesenchymal stromal cells (MSC) could contribute to tumor-supportive cell niche and have been shown to display tumor-specific transcriptomic, phenotypic, and functional features compared to normal tissue. In our study, we investigate whether these two cell subsets establish a bidirectional crosstalk in the context of B-cell lymphoma. We used microarrays to explore how neutrophils could trigger the polarization of tumor-supportive stromal cells.
Project description:The bone marrow is continuously occupied by high numbers of neutrophils, and a tumor-supportive bias of these cells could significantly impact bone marrow-confined malignancies. In multiple myeloma, the bone marrow is characterized by inflammatory stromal cells with the potential to influence neutrophils. Here, we investigated myeloma-associated alterations in marrow neutrophils and the impact of stromal inflammation on neutrophil function. Mature neutrophils in myeloma marrow are activated and tumor-supportive, transcribing increased levels of pro-inflammatory cytokines, including IL-1β, and myeloma cell survival factors, such as the BCMA-ligand BAFF. Neutrophils were re-activated after first-line treatment, while this regimen reduced, but did not normalize, stromal inflammation. Interactions with inflammatory stroma induced neutrophil activation, including BAFF secretion, in a STAT3-dependent manner and once activated, neutrophils gained the ability to reciprocally induce stromal activation. Combined, our data define the presence of a neutrophil-stromal cell feed-forward loop driving tumor-supportive inflammation that could impact disease recurrence.
Project description:The cellular components of the tumor microenvironment (TME) in non-Hodgkin B cell lymphoma demonstrate remarkable diversity. Recent evidence suggests that the spatial organization of malignant, immune and stromal cells within the TME is associated with clinical outcome and response to therapy. Yet, whether tumor cells distribution within the distinct nodal compartments, following lymphatic or hematogenous dissemination further influence the shaping of the TME and the antitumoral immune response remains unclear. We used Bulk RNA sequencing to analyze the diversity transcriptomic profiles of Eµ-myc lymphoma in 3 different conditions.
Project description:Analysis of gene expression levels in non-Hodgkin lymphoma (NHL) cells exposed to neutrophils and chemotherapy. We aimed to see the impact of normal peripheral blood neutrophils on the sensitivity of lymphoma B cells to anticancer agents. The results provide insight into the genes that may be involved in the mechanism by which neutrophils attenuate the sensitivity of lymphoma B cell to chemotherapy.
Project description:Analysis of differential gene expression in human non-Hodgkin`s lymphoma cell lines and a primary leukaemic tumor sample of large cell anaplastic type in comparison with Hodgkin`s lymphoma cell lines and other non-Hodgkin`s lymphoma samples and non-neoplastic lymphocytes Keywords: cell type comparison