INEM - Institut Necker Enfants Malades’ Post

From May 12th to 15th, 2025, the 3rd Electronic Conference on Biomedicines will take place. I am honored to chair Session S4: Immune System, Tumor Immunology, and Autoimmune Disease. https://lnkd.in/dEV-94ej Biomedicines MDPI #immunesystem #autoimmunity #rheumatoidarthritis #tumorimmunology #conference #research #immunology #immunomics

𝐂𝐥𝐞𝐯𝐞𝐫 𝐧𝐞𝐮𝐫𝐨𝐧𝐬 𝐒𝐮𝐛𝐭𝐢𝐭𝐥𝐞: 𝐍𝐞𝐮𝐫𝐨𝐧𝐚𝐥 𝐫𝐞𝐩𝐮𝐫𝐩𝐨𝐬𝐢𝐧𝐠 𝐨𝐟 𝐭𝐡𝐞 𝐓𝐋𝐑𝟗 𝐩𝐚𝐭𝐡𝐰𝐚𝐲 🌍 Those familiar with immunology will surely recognise the TLR (Toll-Like Receptor) and STING (STImulator of INterferon Gene) signalling pathways. Professionals in the field of oncology may be aware of how manipulating these pathways can facilitate the infiltration of immune cells into otherwise immune-deserted tumours (turning cold tumours hot 🔥!), to build an immune response against cancer. 👉 As a genuine (endosomal) DNA sensor, TLR9 detects small fragments of pathogen DNA , specifically unmethylated CpG-containing motifs of bacterial and viral origin, activating immune responses to these pathogens. It is well expressed by dendritic cells, macrophages, NK cells and other antigen presenting cells. 👉 Interestingly, TLR9 is also expressed by neurons. A recent research study published in Nature (Jovasevic V et al., 2024) describes how TLR9 plays a crucial role in the formation and retention of context memories. In certain CA1 hippocampal neurons, a learning stimulus (contextual fear conditioning) causes sustained DNA damage and triggers a DNA repair response in those neurons, which seems required to build stable memory. Pretty interesting. 👉 Now comes the totally unexpected bit. It turns out that TLR9 in those same hipocampal neurons is activated by endogenously generated small non-coding dsDNA fragments (sustained DNA damage, remember?). The results obtained suggest that neurons have repurposed TLR9's original pro-inflammatory role and redirected it to suit their needs. Activated neuronal TLR9 is essential to trigger a DNA repair response around the centrosome and the organisation of individual hippocampal neurons into memory clusters. 👉 Direct consequences of these findings: CNS anti-inflammatory treatment strategies, although beneficial for restricting astrocytic and microglial activation, may prove detrimental for preserving neurocognitive health. I rarely post on topics outside of antibody-based therapies. But this paper struck me so much that I had to share it. Have a nice day of worker! #immunooncology, #inflammation, #memory, #hipocampus, #TLRpathway

I have a CONFESSION to make🤫. I had NO IDEA what is Balb/c mice and why it’s so damn popular in antibody research! So naturally, I had to do some DIGGING: 🔬 The Balb/c mouse strain is a widely used model in biomedical research, particularly in antibody discovery and immunology studies. 🐭 🔬 Developed in the 1920s by Clarence Cook Little and Carl E. Allen at the Jackson Laboratory, Balb/c mice were originally bred for cancer research. 🧬 🔬 The name "Balb/c" for this mouse strain originates from the two original strains it was derived from: "B" for the Balb/c strain and "C" representing its specific substrain. 🐭 “Alb” actually stands for Albino - due to mutation that results in the absence of melanin, leading to their characteristic albino appearance with white fur, pink eyes, and unpigmented skin. Because of that, this is helpful for: 🔍 VISUALIZATION: The lack of pigmentation in Balb/c mice makes it easier to visualize and track certain physiological changes, such as tumor growth or skin-related studies. 🧬 GENETIC BACKGROUND: The albino phenotype is part of the overall genetic background of Balb/c mice, which includes their well-characterized immune system and reproducibility in experiments. ❌ CROSSBREEDING: Because of their albino trait, Balb/c mice are often used in genetic studies and crossbreeding experiments to introduce specific genetic modifications or to study inheritance patterns. 🔬 In antibody discovery, Balb/c mice are often used to generate HYBRIDOMAS, which are immortalized cell lines capable of producing monoclonal antibodies. 💉 🔬 In addition, Balb/c mice are frequently utilized in pharmacokinetic (PK) studies due to their well-characterized genetic background, immune system characteristics such as the TH2 response, and availability from commercial suppliers, ensuring standardization and reliability in research outcomes. 🔬 Overall, Balb/c mice continue to play a crucial role in advancing our understanding of immunology and in developing novel antibody-based therapies. 💊 Do you use Balb/c mice and what experiments are they a part of? #antibodies #biotech #research #mice #antibodytherapeutics

Mitochondrial dynamics controls T cell fate! I saw this phrase sometime ago while I was reading one of the most cited paper on T cell metabolism (https://lnkd.in/ei_G93qG) from the Pearce’s Lab. Ever since then, I have so longed to know more and I get happy to read new papers in the field of T cell metabolism especially in immunology context. I found a paper published today from the Donnadieu’s lab which further underscores the importance of mitochondria in T cell motility in solid malignancies. Does this mean the mitochondria are not just the power house but also the means of transport for T cells? This will definitely open new strategies towards the stimulation of mitobiogenesis especially to combat present hurdles faced in adoptive cell therapy in solid malignancies.

Source: Advances in experimental medicine and biology This article discusses the role of proteomics in understanding the relationship between innate immunity and disease. Proteomics helps identify key proteins involved in infections, cancer, autoimmune disorders, and neurodegenerative diseases. These findings have implications for diagnostics, therapies, and vaccines. Proteomics also reveals innate signatures associated with tumor development, immune evasion, and therapeutic response in cancer research. In autoimmunity, proteomic analysis has identified autoantigens and dysregulation of the innate immune system, providing opportunities for early diagnosis and new therapeutic targets. Similarly, in neurodegenerative diseases like Alzheimer's and Parkinson's, proteomics has identified altered protein expression patterns, offering insights into potential therapeutic strategies. Overall, proteomics of the innate immune system has the potential to revolutionize research and improve patient outcomes in various diseases.

A interesting research about thr comprehensive single-cell RNA sequencing analyses on fibroblast cells from 517 human samples, 11 tissue types • c05-PI16 fibroblasts, primarily found in adjacent normal tissues, can transition into c16-SFRP2 proto-myofibroblasts when exposed to a combination of IL1β and TGF-β. • c05 fibroblasts play a pivotal role in recruiting CD8 memory T cells to perivascular niches, mediated by the CCL5-ACKR4 axis. • c03-COL15A1 fibroblasts, predominant in adjacent normal tissues near the basement membrane, exhibit the capacity to transform into c19-MMP1 fibroblasts upon exposure to IFNs and TGF-β stimulation. • c19 fibroblasts actively contribute to the recruitment and retention of immunosuppressive Tregs and myeloid cells such as LAMP3+ DCs, through intricate ligand-receptor interactions such as ICAM1-IL2RA, and promote the immunosuppressive environment by secreting TGFB1 and IL11. • Both c16, c11, and c19 fibroblast subsets are capable of differentiating into c04-LRRC15 myofibroblasts under the influence of TGFβ. • c04-LRRC15 fibroblasts, in turn, play a role in attracting SPP1+ macrophages, shaping an immune-excluded cell niche through interactions such as SPP1-ITGAV/ITGB1.

🧬 Shedding light on the complexity of hepatic stellate cells (HSCs)… HSCs play a pivotal role in the progression from liver fibrosis to cirrhosis. These diverse cells can perform many functions: 🔸 The "good" – maintaining essential liver functions 🔸 The "bad" – emerging during fibrosis 🔸 And the "ugly" – promoting hepatocellular carcinoma Research published earlier this year describes how scientists, using single-cell RNA sequencing, have mapped this diversity – revealing how HSC subpopulations shift in liver disease states. This balance between protective and harmful cell types can shape disease outcomes, and potential therapeutic avenues. By untangling the different phenotypes between these disease states, we focus on developing RNA therapies targeting genes with the potential to impact liver disease progression in the right cell type, at the right time. Read the paper published in Cellular and Molecular Gastroenterology and Hepatology: https://lnkd.in/gHVc2UKt

🚨 Exciting Research Alert! 🚨 We are thrilled to share a groundbreaking study by Vladyslav Kavaka et al. has been recently published in Science Immunology (Science Magazine). This exciting study explores the intricate role of the C3 complement protein in regulating immune responses within tissues. Using a twin study design, the authors uncovered specific immune cell behaviors that reveal how CD8+ T cells and the complement system influence infections, cancer, and autoimmune disorders. Their findings have significant implications for targeted therapies and precision medicine. This research not only breaks new ground in immune regulation but also opens pathways for earlier diagnostics and future treatments. Check it out here: https://lnkd.in/d9cPyNHS A huge congratulations to Vladyslav Kavaka, Luisa Mutschler, Clara de la Rosa del Val, Klara Eglseer, Ana M Gómez Martínez, Andrea Flierl-Hecht, Betina Ertl-Wagner, Keeser Daniel, Martin M. Mortazavi, @Klaus Seelos, Hanna Zimmermann, @Jürgen Haas, @Brigitte Wildemann, Tania Kümpfel, @Klaus Dornmair, Thomas Korn, @Reinhard Hohlfeld, Martin Kerschensteiner, PD Dr. med. Lisa Ann Gerdes, and Eduardo Beltrán for this remarkable achievement! 👏 It was a pleasure for our team to gain a sneak preview and edit the text before submission. 🔬✨ #ScienceImmunology #Immunotherapy #BiomedicalResearch #ScientificPublishing #AcademicEditing #Immunology #TargetedTherapies #AutoimmuneDiseases #InsightEditingLondon #ScienceBreakthrough

Thrilled to share our research on cutaneous leishmaniasis in The Journal of Immunology. This pivotal study, conducted in Colombia, delves into how the immune response influence the healing of lesions. 🧐 In our study, we analyzed cutaneous lesions in leishmaniasis patients using RNA sequencing to observe the transcriptional dynamics throughout the treatment process. 🚀 We discovered that day 10 is a critical juncture: mechanisms of healing or failure seem to be established early. This insight is vital for guiding more effective early interventions in the future. 💡 Key findings include: in patients who healed, pathways like the formation of the stratum corneum are activated, contrasting with the inhibition in keratinization processes and sustained proinflammatory responses in cases of therapeutic failure. 🌍 This research marks a significant step towards personalizing treatment for leishmaniasis, potentially reducing the long waiting periods and challenges associated with current therapy. Thrilled to have collaborated with Lina Fernanda Giraldo Parra, ADRIANA MARIA NAVAS ZUÑIGA, Ashton Trey Belew, Najib El-Sayed and my mentor Maria Adelaida Gomez on this groundbreaking research. For those interested in exploring our findings on cutaneous leishmaniasis further, you can access the full article here: https://lnkd.in/ePhPqXNy

#Immunotherapy | Targeting of #Tumor-associated #Macrophages: Can we be more clever than #Cancer Cells 🤔 | Time to TAMe #TAMs 👍 | Breaking OPEN ACCESS Review Online Now at Cellular & Molecular #Immunology 👏 | With increasing incidence and geography, cancer is one of the leading causes of death, reduced quality of life and disability worldwide. Principal progress in the development of new anticancer therapies, in improving the efficiency of immunotherapeutic tools, and in the personification of conventional therapies needs to consider cancer-specific and patient-specific programming of innate immunity. Intratumoral TAMs and their precursors, resident macrophages and monocytes, are principal regulators of tumor progression and therapy resistance. This review* summarises the accumulated evidence for the subpopulations of TAMs and their increasing number of biomarkers, indicating their predictive value for the clinical parameters of carcinogenesis and therapy resistance, with a focus on solid cancers of non-infectious etiology. It presents the state-of-the-art knowledge about the tumor-supporting functions of TAMs at all stages of tumor progression and highlight biomarkers, recently identified by single-cell and spatial analytical methods, that discriminate between tumor-promoting and tumor-inhibiting TAMs, where both subtypes express a combination of prototype M1 and M2 genes. The review focuses on novel mechanisms involved in the crosstalk among epigenetic, signaling, transcriptional and metabolic pathways in TAMs. Particular attention has been given to the recently identified link between cancer cell metabolism and the epigenetic programming of TAMs by histone lactylation, which can be responsible for the unlimited protumoral programming of TAMs. Finally, it explains how TAMs interfere with currently used anticancer therapeutics and summarise the most advanced data from clinical trials, which it divides into four categories: inhibition of TAM survival and differentiation, inhibition of monocyte/TAM recruitment into tumors, functional reprogramming of TAMs, and genetic enhancement of macrophages. *https://lnkd.in/en8mCybn Celentyx Ltd #immunooncology www.celentyx.com Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady FIGURE | Functions and mediators of TAMs in tumor progression |