The Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM) pursues its mission of excellence through nationally and internationally recognized research.<\/p>\n\n\n\n
Here you’ll find the scientific publications of recent weeks, the <\/strong>fruit of the work of the center’s teams. They illustrate the richness and diversity of the themes explored in the fight against cancer, from fundamental to translational research. <\/p>\n\n\n\n Headlines<\/p>\n\n\n\n OHIO Department, Nun\u00e8s \/ Devillier team<\/strong><\/p>\n\n\n\n Butyrophilins (BTNs), are molecules involved in the activation of specific cytotoxic T lymphocytes possessing a T cell receptor (TCR) expressing \u03b3 and \u03b4 chains (LT \u03b3\u03b4) in place of the \u03b1 and \u03b2 chains of the more conventional CD4+<\/sup> and CD8+<\/sup> T lymphocyte TCRs. BTNs are expressed at the cell membrane, almost ubiquitously for BTN2A1, and after overexpression mediated by cellular activation or inflammation for BTN3A. These two molecules function as heterodimers, enabling the activation of \u03b3\u03b4 LTs. Recently, these molecules have been studied as novel immune checkpoint (IC) markers, leading to the development of drugs currently in clinical trials (ICT01, Imcheck Therapeutics). However, the regulation of the expression and function of these molecules remains poorly understood. <\/p>\n\n\n\n In our paper, we demonstrated that BTN2A1 expression increases with TCR stimulation, via anti-CD3\/CD28 antibodies, and that this increase is mediated by trogocytosis function in the presence of activated myeloid cells (e.g. monocytes). Trogocytosis characterizes the exchange of cell membrane parts or fragments and associated cytosol. This occurs during cell contacts, which may be due to activation or a pathological process. During trogocytosis, the molecules present on the transferred membrane fragment are preserved. <\/p>\n\n\n\n We have shown that BTN2A1 can be acquired by trogocytosis by BTN2A1-depleted B lymphocytes (BTN2A1-KO) in cocultures with activated monocytes, which express it naturally. We hypothesized that a gain of BTN2A1 at the cell membrane via trogocytosis might induce enhanced sensitivity to LT \u03b3\u03b4, and this is what we demonstrated. Indeed, normal or tumor cells that had acquired BTN2A1 via trogocytosis were more sensitive to lysis by LT \u03b3\u03b4 when we measured cell death by Caspase 3 and 7 production. Finally, we demonstrated BTN2A1 acquisition by circulating lymphocytes, via monocyte activation, in a cohort of 87 endometrial cancer patients. <\/p>\n\n\n\n Our study has revealed a new aspect of the regulation of BTN2A1 expression and functions, as well as the importance of trogocytosis in the regulation of CI expression in pathophysiology. Indeed, trogocytosis is a mechanism which, under physiological conditions, could participate in the elimination of autoreactive lymphocytes by \u03b3\u03b4 LTs. In pathology, and particularly in oncology, this acquisition of BTN2A1 could induce better tumor elimination after treatment. It is also becoming important to consider the effect of trogocytosis in supervised analyses, where there is a tendency to exclude markers that “don’t belong” to a cell type or are considered aberrant. OHIO Department<\/strong><\/p>\n\n\n\n Nun\u00e8s \/ Devillier team<\/strong><\/p>\n\n\n\n<\/i> V\u03b39V\u03b42 T Cells Express an Antitumor Profile Associated with Anti-PD-(L)1 Responses and Activation Defects Restored by Anti-BTN3A in Triple-Negative Breast Cancer.<\/a>\n\n<\/i> Improving transparency and empowerment for cancer patients by accessing their full online personal medical records.<\/a>\n\n<\/i> Tremelimumab plus durvalumab combined to metronomic oral vinorelbine: Results from the breast cancer cohort of the phase II MOVIE study.<\/a>\n\n\n\n Duprez team<\/strong><\/p>\n\n\n\n<\/i> Assessment of Systematic JAK2V617F Screening in 996 Patients With Venous Thromboembolism.\n<\/a>\n\n<\/i> Ectopic expression of BEX genes in T-cell Acute Lymphoblastic Leukemia.\n<\/a>\n\n\n\n De Sepulveda team<\/strong><\/p>\n\n\n\n<\/i> Dual targeting of CDK6 and LSD1 is synergistic and overcomes differentiation blockade in AML.\n<\/a>\n\n\n\n Team Aurand-Lions<\/strong><\/p>\n\n\n\n<\/i> Junctional adhesion molecule-C: A multifunctional mediator of cell adhesion.\n<\/a>\n\n\n\n Translate-it Department<\/strong><\/p>\n\n\n\n Team Dusetti \/ Iovanna<\/strong><\/p>\n\n\n\n<\/i> Toward Precision Chemotherapy for Pancreatic Cancer Guided by Transcriptomic Signatures.\n<\/a>\n\n<\/i> The mitochondrial catastrophe induced by NUPR1 inhibitors as a novel strategy to fight against cancer.\n<\/a>\n\n<\/i> Mechanisms of induced resistance to the antitumoral agent ZZW-115 in pancreas ductal adenocarcinoma.\n<\/a>\n\n<\/i> Understanding the heterogeneity of pancreatic ductal adenocarcinoma.\n<\/a>\n\n<\/i> The intrinsically disordered protein NUPR1 binds to phospholipids.<\/a>\n\n<\/i> Self-assembling dendrimer nanodrug formulations for decreased hERG-related toxicity and enhanced therapeutic efficacy.<\/a>\n\n\n\n Benzekry \/ Ciccolini team<\/strong><\/p>\n\n\n\n<\/i> Dihydropyrimidine Dehydrogenase-Guided Dosing of 5-Fluorouracil: Prioritizing Precision Over Dose Reduction.<\/a>\n\n<\/i> Cross-Species Extrapolation of Neonatal Fc Receptor (FcRn) Binding Affinity to Predict Monoclonal Antibody Pharmacokinetics in Humans Using Physiologically Based Pharmacokinetic Modeling (PBPK): Are We There Yet?<\/a>\n\n<\/i> [Autoimmune diseases and immunotherapies].<\/a>\n\n<\/i> DPD Ultra-Rapid Metabolizer Status and Efficacy of 5-Fluorouracil Treatment: A Real-World Study.<\/a>\n\n\n\n Mamessier \/ Bertucci team<\/strong><\/p>\n\n\n\n<\/i> Expression of antibody-drug conjugate targets in soft tissue sarcomas.<\/a>\n\n<\/i> Gene expression-based rationale for investigating CDK4\/6 inhibitors in primitive myelofibrosis.<\/a>\n\n<\/i> Is adjuvant chemotherapy beneficial in NSCLC patients over 75? Insights from a retrospective analysis. <\/a>\n\n\n\n Team Pasquier \/ Andr\u00e9<\/strong><\/p>\n\n\n\n<\/i> Near Complete Response With Trastuzumab Deruxtecan in a Teenager With Relapsing Metastatic Desmoplastic Small Round Cell Tumor.<\/a>\n\n\n\n Genome integrity department<\/strong><\/p>\n\n\n\n Team Lachaud<\/strong><\/p>\n\n\n\n<\/i> TERT expression attenuates metabolic disorders in obese mice by promoting adipose stem and progenitor cell expansion and differentiation.<\/a>\n\n\n\n Pag\u00e8s team<\/strong><\/p>\n\n\n\n<\/i> The RecBC complex protects single-stranded DNA gaps during lesion bypass.\n<\/a>\n\n\n\n The Coulon team<\/strong><\/p>\n\n\n\n<\/i> [Towards an ever more precise, integrated, and anticipatory management of breast cancer].\n<\/a>\n\n<\/i> Toxicity Profiles of Antibody-Drug Conjugates: Synthesis and Graphical Insights to Optimize Patient-Centered Treatment Strategies for HER2-Negative Metastatic Breast Cancer.\n<\/a>\n\n<\/i> [Antibody-drug conjugates in breast cancer: Resistance mechanisms and prospects].<\/a>\n\n<\/i> [Breast cancer in women of childbearing age: Issues surrounding the role of hormones].<\/a>\n\n\n\n COMET Department<\/strong><\/p>\n\n\n\n Team Maina<\/strong><\/p>\n\n\n\n<\/i> Establishment of a mouse hepatocellular carcinoma tumoroid panel recapitulating inter- and intra- heterogeneity for disease modelling and combinatorial drug discovery.<\/a>\n\n<\/i> The HDAC inhibitor romidepsin renders liver cancer vulnerable to RTK targeting and immunologically active.<\/a>\n\n\n\n Team Charafe \/ Ginestier<\/strong><\/p>\n\n\n\n<\/i> The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.<\/a>\n\n<\/i> The LRP4\/YAP axis drives the radiation-tolerant persister (RTP) cell state in breast cancer.<\/a>\n\n\n\n Team Zimmermann<\/strong><\/p>\n\n\n\n<\/i> Syntenin Controls Extracellular Vesicle-Induced Tumour Migration by Regulating the Expression of Adhesion Proteins on Small Extracellular Vesicles.<\/a>\n\n\n\n
And also…<\/p>\n\n\n\n