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🔴🔵⚪ CALL for CONTRIBUTION: Recent Advances in Glycosylation Patterns in Cancer and Their Implications 1️⃣ Cancer-Related Changes in Glycosylation: 🔸Alteration in glycan biosynthesis pathways in cancer cells and their connections to diagnosis, clinical outlook, genetic factors, and the functional role of glycans in cancer biology have recently drawn great attention in cancer therapy. 2️⃣ Early Evidence of Altered Glycosylation in Cancer: 🔸Monoclonal antibody technology identified "tumor-specific" antibodies targeting glycan epitopes, often associated with "oncofetal antigens" expressed on tumor cells and embryonic tissues. 3️⃣ Diverse Forms of Glycan Alterations: 🔸Glycan changes in malignant cells take various forms, including loss or excessive expression of specific glycans, increased incomplete or truncated glycans, and the emergence of novel glycans. 4️⃣ Potential Therapeutic Approaches: 🔸Interest in targeting glycan-dependent molecular interactions to enhance immune checkpoint inhibition is growing. 🔸N-glycosylation stabilizes the PD-L1 checkpoint molecule and facilitates recognition by PD-1, making therapeutic interventions aimed at disrupting PD-L1 glycosylation promising. 🔸Strategies are being developed to block or remove tumor cell sialic acid ligands for Siglecs using sialic acid mimetics or targeted delivery of sialidases. 🔸Some Siglecs on hematopoietic cancer cells, like Siglec 2, can be targeted for CAR-T cell immunotherapy or cytotoxic drug delivery. 🔸The manipulation of glycans and glycan-binding proteins holds significant promise in modulating anti-tumor immunity due to their established roles in regulating the broader immune response. ✅ We are excited to announce a special issue in Frontiers in Immunology dedicated to recent advancements in glycobiology, specifically focusing on systems glycobiology and its impact on understanding health and diseases, including cancer. 🔴 We invite researchers, scientists, and experts in the field of glycobiology to contribute their original research, reviews, and perspectives to this special issue. ☑ Why Choose Frontiers in Immunology? 🔹Frontiers in Immunology is a prestigious Q1 journal with an impressive impact factor of 7.3, providing high visibility for your research. Submit your manuscript via ➡ https://lnkd.in/gerrtg3V Dr. Adeyinka A.A. Payam BEHZADI BSc, MSc, PhD American Association for Cancer Research European Association for Cancer Research (EACR) Iran Stem Cell Association (ISCA) Dr. Syeda Zubeda Harvard University Elham Hosseinzadeh Harvard Medical School Broad Institute of MIT and Harvard M. Ghadamgahi Novartis Institutes for BioMedical Research (NIBR) Mohammad Owais Ansari Universiti Putra Malaysia UT Southwestern Medical Center Vida Tajiknia Charalampos Proestos #GlycosylationPatterns #CancerResearch #Immunotherapy #BiomarkerDiscovery

Let’s talk about some notable recent breakthroughs in #immunooncology, starting with the I-SPY clinical trials for #breastcancer. 🩺 Over recent decades, many patients have benefitted from targeted treatments against amplified HER2, estrogen receptor (ER), and/or progesterone receptor (PR). However, “triple negative” breast cancer (TNBC) tumors lacking these targets have been more challenging to treat. 𝗜-𝗦𝗣𝗬𝟮 𝗵𝗮𝘀 𝘁𝘄𝗼 𝗸𝗲𝘆 𝗮𝗶𝗺𝘀: 💉To assess the efficacy of promising cancer treatments (including anti-PD1 pembrolizumab) as neoadjuvant therapies, in combination with chemotherapy and surgery 🔬To identify new biomarkers that are indicative of response, allowing more accurate predictions of treatment success for individual patients in the future. 𝗧𝗵𝗶𝘀 𝘁𝗿𝗶𝗮𝗹 𝗶𝘀 𝗶𝗺𝗽𝗼𝗿𝘁𝗮𝗻𝘁 𝗳𝗼𝗿 𝘀𝗲𝘃𝗲𝗿𝗮𝗹 𝗿𝗲𝗮𝘀𝗼𝗻𝘀: 🧪While specific therapies are provided to each patient, based upon their traditional subtype classifications, the trial co-ordinators are aiming to develop a more targeted, personalized approach to breast cancer treatment, retrospectively assessing detailed molecular features and identifying the drugs that performed best 📊The trial co-ordinators and sponsors have made the molecular data freely available, allowing researchers to identify further response biomarkers and ultimately improve the range of available treatments 📈The data show positive results, particularly for TNBC. Approximately 2/3 of TNBC patients responded to pembrolizumab – a great outcome demonstrating the power of immune checkpoint blockade – however, when patients were retrospectively re-classified, the HER2-/immune-enriched tumours showed a pathological complete response in nearly 4/5 patients, suggesting these biomarkers could be used for future patient selection. 🧬A more recent analysis presented at AACR2024 showed that in HER2- breast cancer patients, high levels of IL-12 cytokine signaling before treatment were associated with an improved pathological complete response rate across several therapies, including pembrolizumab. Given our oNKo-001 and oNKo-044 programs - which use affinity-optimized IL-12 to drive localized inflammation within the tumour - we found this last result particularly exciting! 👏 Read more about this amazing work in their recent abstract here 👇https://lnkd.in/g3qxm8Qe More information and links are also provided in the comments section! Laura Esserman Quantum Leap Healthcare Collaborative #cancerresearch #cancerclinicaltrials #triplenegativebreastcancer

🟡🔴 Neutrophil-activating therapy for the treatment of cancer Follow for more 👉 #MD_Immunol https://lnkd.in/ewNq6iGe 💠 On the basis of the findings reported here, we propose a multistep mechanism by which neutrophils can be harnessed to eradicate multiple types of tumors. 1️⃣ TNF signals through TNFR1 to induce neutrophil recruitment and activation in the tumor. 2️⃣ Anti-CD40 promotes neutrophil cytotoxicity and granulopoiesis. 3️⃣ And tumor-binding antibody enhances tumor clearance through FcγR-mediated ADCC, potentially by trogocytosis. 👉💠 See figure 💠 So treatment with TNF, a CD40 agonist, and a tumor-binding antibody activates neutrophils to eradicate tumors. 💠 Further research showed that the neutrophils kill tumor cells by stimulating the production of molecules called reactive oxygen species, which damage DNA and proteins and can cause cell death. 💠 On the other hand T cells, in attacking the tumors, activated a swarm of neutrophils - which in turn killed the tumor cells that the T cells could not eliminate. 💠 T cell-educated neutrophils can eliminate these 'invisible' tumor cells. This discovery highlights the importance of mobilizing multiple arms of the immune system in the fight against cancer.” 💠 Complement component C5a activates neutrophils to produce leukotriene B4, which stimulates reactive oxygen species production via xanthine oxidase, resulting in oxidative damage and T cell-independent clearance of multiple tumor types.( Neutrophil C5aR1 signaling stimulates LTB4 release, driving ROS production via XO). 💠 Neutrophil-mediated oxidative damage drives T cell-independent tumor clearance. 💠These data establish neutrophils as potent anti-tumor immune mediators and define an inflammatory pathway that can be harnessed to drive neutrophil-mediated eradication of cancer. 💠 Intratumoral TNF + anti-CD40 + anti-tumor antibodies induce an inflammatory cascade. 💠 Inhibition of receptors on neutrophils has been shown to slow tumor growth by inhibiting pro-tumor functions of neutrophils such as the promotion of angiogenesis and T cell suppression. 💠 Additionally, inhibition of certain suppressive signals can enhance killing of tumor cells by neutrophils ex vivo, induce modest reductions in tumor growth, and promote activation of CD8+ T cells or NK cells to inhibit tumor growth. 💠As we know neutrophils can also kill antibody-bound tumor cells and mediate the effects of monoclonal antibody (mAb) therapy initiated concurrently with tumor engraftment. 👉💠 The researchers now are continuing to study these anti-tumor neutrophils, to determine how they can best be induced and directed – as cancer fighters on their own, or as enhancers of other immunotherapies. #immunology #Neutrophils #cancer  #immunotherapy

Anti-CD5 CAR-T cells with a tEGFR safety switch exhibit potent toxicity control The three patients reported here were part of the Investigator-Initiated Trial (IIT) (NCT04767308) that evaluated the safety and efficacy of genetically edited autologous anti-CD5 CAR-T cells in the treatment of r/r CD5 positively expressing hematologic malignancies. Patient 1 is a 47-year-old female who was diagnosed with angioimmunoblastic T cell lymphoma (AITL) and had progressive disease (PD) status at enrollment. Patient 2 is a 49-year-old male with AITL and had stable disease (SD) status at enrollment. Patient 3 is a 31-year-old female with subcutaneous panniculitis-like T cell lymphoma (SPTCL) and had a PD status at enrollment (Table S1). The CAR construct comprised biepitopic, fully human-derived CD5-targeting nanobodies, 4-1BB costimulatory element, CD3ζ activation domains, and a tEGFR switch connected by a peptide of Thosea asigna virus [2]. The manufacturing process of anti-CD5 CAR-T cells, including leukapheresis collection, T cell isolation and activation, Cas9 ribonucleoprotein (RNP) mediated CD5 gene deletion, CAR gene-carrying lentivirus transduction, CAR-T cell expansion, formulation and cryopreservation is shown in Fig. S1. This study was approved by the institutional review board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and the assessments of adverse effects were conducted strictly according to the National Cancer Institute (NCI) and American Society for Transplantation and Cellular Therapy criteria (ASTCT). In this study, the kinetics of CAR-T cells in peripheral blood were monitored by drop digital polymerase chain reaction (ddPCR) and flow cytometry. Natural killer (NK) cells and neutrophils were detected by flow cytometry, and inflammatory cytokines and acute phase proteins in plasma were detected by chemiluminescence and turbidimetric inhibition immunoassay respectively.

Our customers have published a research paper titled “Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy” on Signal Transduction and Targeted Therapy. Colorectal cancer (CRC) ranks third in incidence and second in cancer-related mortality worldwide, according to the global cancer statistics in 2020. Processing Bodies (PBs) are known to form through the co-assembly of RNAs with RNA binding proteins (RBPs), notably with mRNA degradation machinery components or ribonucleoproteins (RNPs), involving in mRNA decay and translational repression. In this study, researchers identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. The team’s findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC. Fluorescent in Situ Hybridization Kit used in this study were obtained from GenePharma. For more information, please visit: https://lnkd.in/gyR4PK_d

#INCB086550 is an #Orally Active #PD-L1 Inhibitor for #Multiple Cancers Research   Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell #checkpoint and plays a central role in regulating T cell exhaustion. PD-L1 is a 40 kDa type 1 transmembrane protein. PD-1 is a member of a family of immunoglobulin domain (#Ig) co-receptors that modify the outcome of activation of the T cell receptor by an antigen-presenting cell (#APC) or infected target cell. PD-1 receptor delivers inhibitory checkpoint signals to activated T cells upon binding to its ligands PD-L1 and PD-L2 expressed on antigen-presenting cells and cancer cells, resulting in suppression of T-cell effector function and #tumor #immune #evasion. Inhibiting the PD-1/PD-L1 #pathway is an attractive strategy for tumor #immunotherapy.   #INCB086550 is a potent, selective, and #orally active #PD-L1 inhibitor, which binds with high #affinity to #PD-L1. #INCB086550 is selective for PD-L1 over PD-L2. #INCB086550 interacts with #human, #cynomolgus, and #rat but not #mouse PD-L1.   In #vitro, #INCB086550 selectively and potently blocks the PD-L1/PD-1 interaction, induces PD-L1 dimerization and internalization. INCB086550 promotes the dimerization of cell-surface PD-L1 and induces PD-L1 entry into Golgi vesicles then traffick to the nucleus. Therefore, the ability of tumor cells to initiate the immunosuppressive effects of the PD-1 pathway in T cells can be eliminated. INCB086550 induces stimulation-dependent cytokine production in primary human immune cells. In #vivo, INCB086550 reduces tumor growth in CD34+ humanized mice and induced T-cell activation gene signatures. INCB086550 shows antitumor efficacy, with increased immune activation and tumor growth control.   Taken together, INCB086550 is a selective and orally active PD-L1 inhibitor with antitumor efficacy.     https://lnkd.in/gutuHmxH   For detailed information: https://lnkd.in/gwqQwq4g

Developing new CAR-T therapies against each hematologic cancer can be technical-challenging and time-consuming. Why not develop a universal CAR-T targeting the conserved antigen across all the hematologic cancers? A bold and mind-blowing Science Translational Medicine paper is out by Nils Wellhausen et al. at Carl June/Saar Gill Laboratory from the University of Pennsylvania. By targeting CD45 as a conserved antigen, Nils Wellhausen et al. developed the CAR45-T cells that efficiently kill hematologic cancers, and, not surprisingly, B cells, T cells, hematopoietic stem cells, and even CAR-T cells, as they all express CD45. To avoid the fratricide on the CAR-T cells while preserving the fitness function of CD45, the authors mapped the CAR targeting epitope on the CD45 D1 domain and performed base editing to create a mutant CD45 (epitope editing) that can no longer be recognized by the anti-CD45 CAR. The epitope-edited CD45 is functional while abrogating the recognition by the CAR45. They showed that the epitope-edited CAR45-T cells are safe and fully functional in killing cancer cells in vitro and in vivo while avoiding fratricide. To reconstitute the hematopoietic cells, the authors applied the same epitope-editing strategy to HSCs’ CD45 and engrafted edited HSCs before the CAR45-T cells treatment. More interestingly, with the proof of similar tumor control by the anti-CD3 and anti-CD45 bispecific T cell engager (BiTE), this strategy has shown pan-hematologic cancer potency and long-term protection while preserving the HSC function. To me, it will be crucial to assess the safety of this pan-hematologic cancer strategy and the HSCs engraftment kinetics and efficiency. Also, the long-term effect of epitope-edited CD45 is to be determined. Still, seeing such an innovative strategy conceived and vigorously tested by carefully designed experiments is always inspiring!

🟨🟪 𝐁𝐢𝐨𝐦𝐚𝐫𝐤𝐞𝐫𝐬 𝐟𝐨𝐫 𝐄𝐚𝐫𝐥𝐲 𝐃𝐞𝐭𝐞𝐜𝐭𝐢𝐨𝐧 𝐨𝐟 𝐂𝐚𝐧𝐜𝐞𝐫: 𝐌𝐨𝐥𝐞𝐜𝐮𝐥𝐚𝐫 𝐀𝐬𝐩𝐞𝐜𝐭𝐬 👉#MD_Immunol welcome to learn more online ⬇️ https://lnkd.in/d-2vdVga 💠 Cancer is a leading cause of death worldwide, and early detection is crucial for improving patient outcomes. 💠 Researchers are focusing on : 🔹️Developing low-cost 🔹️High-throughput 🔹️Early detection tools with high selectivity and specificity for cancer detection. 💠 These biomarkers are typically found in tissues or body fluids and can be produced by cancer cells or normal cells in response to cancer. Presently cancer biomarkers are the backbone of therapy, with greater efficacy and better survival rates. 💠They may include germline or somatic genetic variants, epigenetic signatures, transcriptional changes, and proteomic signatures. 💠They can be detected through non-invasive methods, such as blood tests, making them more accessible and less invasive than traditional screening methods.  💠The purpose of these biomarkers is to detect cancer in otherwise healthy patients, without any signs of disease, and without having shown any signs of disease. 💠 It's noteworthy, Liquid biopsy has shown good potential in detecting circulating biomarkers from any bodily fluid, including peripheral blood, urine and cerebrospinal fluid, ascites, pleural effusion, etc., and includes a genomic, proteomic and metabolite assessment. It is a quick, easy and inexpensive method with minimal invasiveness, making it widely accepted by patients, without major side effects. 💠 Molecular biomarkers for early detection of cancer, including: 🔶️ Autoantibodies: They have shown promise in detecting cancer at early stages, particularly in ovarian cancer 🔶️ ctDNAs: Circulating tumor DNA (ctDNA) is DNA that is released into the bloodstream by cancer cells. ctDNAs have shown promise in detecting cancer at early stages, particularly in lung cancer . 🔶️ miRNAs: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. They have shown promise in detecting cancer at early stages, particularly in breast cancer. 🔶️ DNA methylation: DNA methylation is a process that modifies DNA and can affect gene expression. It has shown promise in detecting cancer at early stages, particularly in colorectal cancer. 🔶️ Protein biomarkers: Protein biomarkers, such as PSA for prostate cancer and CA-125 for ovarian cancer,  However, their specificity and sensitivity are limited, and they are not suitable for all types of cancer 🔶️ Extracellular vesicles 💠 Molecular biomarkers have the potential to provide more accurate and specific cancer detection than traditional screening methods, such as imaging and biopsy. 💠 It is noteworthy further research is needed to fully elucidate the mechanisms of these biomarkers and to determine their safety and efficacy in clinical trials. #immunology #cancer #biomarkers #Liquid #biopsy

Interferon-stimulated neutrophils as a predictor of immunotherapy response Context: Anti-cancer immunotherapies have been nothing short of an outstanding success but despite this, only particular subsets of patients show a durable response to treatment. Predictive biomarkers are pivotal in determining response to such therapies including immune checkpoint inhibitors (ICIs), however current biomarkers for ICI response are limited by their predictive power and tumour intrinsic nature. As such, there is a need for more accurate and accessible predictive biomarkers to support our advancements in precision immuno-oncology and ultimately, improve patient response. Paper summary: This is a really interesting paper published recently where the authors discovered interferon-stimulated Ly6Ehi neutrophils as a blood borne predictive biomarker of immunotherapy response in both humans and mice (AUC ≈ 0.9 in humans). Further, they revealed a 15-gene Ly6Ehi signature that stratifies responders and non-responders in human. The gene signature was identified by analysis of publicly available bulk RNA-seq datasets taken pre-treatment from patients with 6 different cancer types who underwent ICI therapy (n=1,237). In all samples analysed bar one, enrichment of this gene signature correlated strongly with patients who responded to immunotherapy (average AUC > 0.9).   While further clinical validation is required, the paper provides evidence for the potential future use of Ly6Ehi neutrophils as a "pan-cancer" predictive biomarker that can be utilised in a cost effective manner via liquid biopsy! 😀