es/iode’s Post

4 of the authors of this study are UCMC's very own Dr. Sweiss, Dr. Chen, Dr. Nanda, and Dr. Cozen KEY TAKEAWAY: Glucocorticoid receptors (GR), may affect the body's immune response. In triple-negative breast cancer (TNBC) researchers found that higher levels of GR in tumors were linked to an increased presence of immune cells that suppress the immune system. These immune cells, such as regulatory T cells (Tregs) and certain types of dendritic cells, can prevent the body's immune system from attacking the cancer effectively. This means that tumors with higher GR expression may be better at hiding from the immune system, which could make the cancer more likely to relapse or spread. The researchers suggest that blocking GR activity could help reduce this immune suppression, allowing the immune system to fight the cancer more effectively. By targeting GR and the immune cells it affects, treatments could potentially be developed that improve outcomes for patients with TNBC. However, the study notes that more research is needed to understand the full impact of GR on the immune environment and to test these ideas in larger groups of patients. https://lnkd.in/gcmSC6k9

#Immunotherapy | #ProstateCancer | #Sialoglycoproteins suppress Immune Cell #Killing by binding to to selective #Siglecs | #CD59: a targetable Siglec 9 ligand for #Immunotherapy | Now at The Journal of Clinical Investigation | Prostate cancer is the second leading cause of male cancer death in the U.S. Current immune checkpoint inhibitor-based immunotherapies have improved survival for many malignancies; however, they have failed to prolong survival for prostate cancer. Siglecs (sialic acid-binding immunoglobulin-like lectins) are expressed on immune cells and regulate immune responses and function. Siglec-7 and Siglec-9 contribute to immune evasion by interacting with their ligands. However, the role of Siglec-7/9 receptors and their ligands in prostate cancer remains poorly understood. Here*, Ru M Wen, Jessica Stark, G. Edward Wen Marti, et al find that Siglec-7 and Siglec-9 are associated with poor prognosis in prostate cancer patients, and are highly expressed in myeloid cells, including macrophages, in prostate tumor tissues. Siglecs-7 and -9 ligands were expressed in prostate cancer cells and human prostate tumor tissues. Blocking the interactions between Siglec-7/9 and sialic acids inhibited prostate cancer xenograft growth and increased immune cell infiltration in humanized mice in vivo. Using a CRISPRi screen and mass spectrometry, we identified CD59 as a candidate Siglec-9 ligand in prostate cancer. The identification of Siglecs-7 and -9 as potential therapeutic targets, including CD59/Siglec-9 axis, opens up opportunities for immune-based interventions in prostate cancer. *https://lnkd.in/dJ3kCK3S Celentyx Ltd #immunooncology www.celentyx.com Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady GRAPHICAL ABSTRACT

Researchers from the Francis Crick Institute, the National Cancer Institute of the US National Institutes of Health and Aalborg University in Denmark have revealed that vitamin D encourages the growth of a type of gut bacteria in mice, which provides better cancer immunity. The study published in Science found that vitamin D increases the amount of Bacteroides fragilis, providing better immunity to cancer in mice with transplanted tumours. Cancer, including female breast, lung, bowel and prostate cancers, was responsible for more than 18 million new cases worldwide in 2020, according to Cancer Research UK. After giving mice a diet rich in vitamin D, researchers discovered they had better immune resistance to experimentally transplanted cancers and improved responses to immunotherapy treatment. Furthermore, this effect was seen when gene editing was used to remove a protein that binds to vitamin D in the blood and keep it away from tissues. Researchers found that vitamin D acts on epithelial cells in the intestine and increases the amount of a bacteria known as Bacteroides fragilis, which offered mice better immunity to cancer as the transplanted tumours didn’t grow as much. After giving mice Bacteroides fragilis, researchers observed better resistance to tumour growth compared to mice on a vitamin D-deficient diet. Previous, inconclusive research has already suggested a link between vitamin D deficiency and cancer risk in humans. Researchers explored this link by analysing a dataset from 1.5 million people in Denmark, which highlighted a link between lower vitamin D levels and a higher risk of cancer. Read more: https://lnkd.in/gnrx_X5a Stay in touch with all the leading stories, events and opportunities by subscribing to our LinkedIn Newsletter:https://bit.ly/3RbdKtc or joining some of the largest groups most relevant to you: https://bit.ly/4caKquL (A-Z list)

A paper depicting a macrophage-T cell immunity cycle? Yes! We have been showing this type of cancer-immunity cycle interpretation for a very long time, so it's wonderful to see a similar representation independently developed. Effective immune response requires coordination between multiple cell types. The study by van Elsas et al. shows how activated T cells recruit and activate specific macrophages within tumors (M1-like) - a somewhat unnatural feat where T cells are the initiators of the immune response. Activated macrophages play a crucial role in controlling tumors in mice treated with immunotherapy. A macrophage population with the same gene expression signature in human tumors that respond well to immunotherapy is described. https://lnkd.in/ebCVbySw The study gives a huge boost to strategies that can functionally activate tumor-infiltrating macrophages that are capable of inducing leukocyte infiltration and activation (which will include T cells). #immunotherapy #macrophages #T_cells #immunity #immunology #immunooncology #cancer

Immunotherapy-induced CD8+ T cells summon macrophages via CCR5 signaling. Activated T cells skew macrophages into late-stage activated M1-like macrophages. Late-stage activated M1-like macrophages are critical for effective tumor control #immunotherapy #macrophages #CCR5 #M1 #phase1

A research team from UC Irvine has discovered that aligning cancer immunotherapy with the circadian clock enhances the efficacy of checkpoint inhibitor treatments. The circadian clock regulates daily rhythms in bodily processes, including immune function. Optimizing therapy delivery based on an individual's circadian patterns opens new avenues for cancer prevention and treatment. Disruptions in the internal biological clock are linked to a higher risk of certain cancers. Proper regulation of circadian rhythms is essential for suppressing inflammation and supporting immune function. Alterations in the circadian clock can lead to increased inflammation, immunosuppressive myeloid cells, and cancer progression. Administering immunotherapy when immunosuppressive myeloid cells are most abundant significantly enhances the efficacy of immune checkpoint blockades. Future research should explore additional factors and cell types that influence the time-of-day response to checkpoint inhibitor therapy. https://lnkd.in/eEUepfSn

🔬 Exciting advancements in cancer immunology! I recently came across a fascinating study published in Cancer Cell titled “Interleukin-1α Release During Necrotic-like Cell Death Generates Myeloid-driven Immunosuppression That Restricts Anti-Tumor Immunity.” This study challenges the traditional notion that necroptosis—a form of programmed cell death—promotes anti-tumor immunity. Instead, it reveals that inducing necroptosis within tumors creates an immunosuppressive myeloid microenvironment through the release of interleukin-1α (IL-1α), leading to suppressed T-cell function and enhanced tumor growth. Key findings include: • IL-1α released during necroptosis reprograms the tumor microenvironment, limiting immune responses. • Neutralizing IL-1α improves CD8+ T cell recruitment and function, enhancing the efficacy of chemotherapy and PD-1 blockade in preclinical models. • Patients with lower IL1A levels show better outcomes, particularly when treated with chemotherapy. This groundbreaking research highlights a new therapeutic avenue: targeting IL-1α to overcome immune suppression and improve responses to cancer treatments. As someone passionate about the interplay between cell death pathways and cancer, I’m inspired by how this work sheds light on the immune consequences of necroptosis. For anyone exploring immune modulation in cancer therapy, this is a must-read! 👉 Read the full article here: 

Cancer cells as they’re growing also pump out metabolic byproducts into their surrounding environment…but at ‘greater’ quantities than normal cells. Researchers are now looking to see how these metabolic byproducts could be ‘dampening’ the response of the immune system. “Exhausted” T-cells are immune cells that have slowly started to lose their ‘zeal’ in dealing with cancer cells…not being able to ‘dispose’ of them as quickly or robustly as they had been. Researchers at University of Pittsburgh & UPMC Hillman Cancer Center decided to start looking at metabolic byproducts & exhausted T-cells. They found that in the exhausted T-cells, there were more receptors for uptake of lactic acid than ‘non-exhausted’ T-cells. Lactic acid is one of the byproducts that cancer cells pump out…and other cells in the region ‘take’ up…but the only ‘cells’ that can break it down properly & quickly—are the cells of the liver & kidneys. So…when immune cells take up lactic acid, it puts a ‘drain’ on the energy reserves of the cell. When a specific protein (MCT11, an soluble carrier protein for lactic acid) was blocked in ‘exhausted’ T-cells, these cells gained a ‘new’ lease on life…being able to go after cancer cells & had improved functionally. When this protein was blocked (either through use of an antibody or knockdown) in mice models of different cancers—there was improved functionality of the T-cells & tumors were reduced in size for different cancers—such as melanoma, colorectal carcinoma, & head & neck cancers. MCT11 could become an ‘exclusive’ therapeutic target…as it usually exclusively expressed in exhausted T-cells (due to their close proximity to the cancer cells & uptake of the lactic acid). It will be interesting to see if MCT11 does become an therapeutic target for cancer treatments (either alone or in combination with other immunotherapies), and it will also be interesting to see what other metabolic carrier proteins could also be ‘targeted’ within different ‘exhausted’ immune cells. #cancerresearch #metabolites #lacticacid #tcells #animalmodels 

Personalized Cancer Vaccines: A Revolutionary Leap in Defeating Cancer The fight against cancer is entering a groundbreaking era, thanks to personalized cancer vaccines—a new frontier in treatment that’s bringing hope to millions. These innovative therapies work by training the immune system to recognize and attack the unique mutations in a patient's tumor, called neoantigens. Unlike preventive vaccines, personalized cancer vaccines are designed to eliminate residual cancer cells after treatments like surgery or chemotherapy, significantly reducing the risk of recurrence. Recent Breakthroughs in Cancer Vaccines: Moderna’s mRNA Vaccine: Initially successful in melanoma, it’s now showing promise in HPV-negative head and neck cancer. Results include tumor control in multiple patients and two complete remissions. TG4050 by Transgene: In combination with surgery and traditional therapies, this vaccine achieved zero recurrences in head and neck cancer patients after more than a year of follow-up. BioNTech & Genentech’s Pancreatic Cancer Vaccine: In early trials, patients showed robust immune responses and lower recurrence rates, with a larger trial underway. Why This Matters: Cancer is complex, and its recurrence often poses the greatest challenge. Personalized cancer vaccines are tailored to the individual, offering targeted solutions that could change outcomes for even the deadliest cancers. While still in early stages, the results are incredibly promising. With advancements in mRNA technology and cancer biology, the potential to revolutionize cancer treatment feels closer than ever. Let’s continue to support the incredible research that’s turning the tide against humanity’s greatest killer. #CancerResearch #InnovationInHealthcare #mRNA #CancerVaccines #PersonalizedMedicine #MedicalLaboratoryTechnology #Microbiology #Phlebotomy #LaboratoryTesting #DiagnosticTesting #HealthcareProfessional #MedicalTesting #ClinicalLaboratory #BiomedicalScience #HealthcareIndustry #MedicalScience #LaboratorMedicine #ClinicalMicrobiology #InfectionControl #PhlebotomyTechnician #MedicalLabTechnician #MicrobiologyLab #ClinicalLab #HealthcareCareer #MedicalCareer #ScienceCareer #COVID19Testing #Virology #Bacteriology #Parasitology #MolecularDiagnosis #GeneticTesting #Cytology #Histopathology #Immunology #Serology

💎💎Whatsapp!! 💎💎Antibiotics Against Cancers Antibiotics reveal a new way to fight cancer Researchers from Osaka University found that #tetracycline #antibiotics stimulate T lymphocytes in the body’s #immune #system to attack and destroy #cancer cells. The antibiotics work by blocking the action of #galactin-1, a #protein made by cancer cells that #suppresses the immune system. Identification of this new target may lead to the development of novel cancer #immunotherapies. Cancer cells grow and spread by hiding from the body’s immune system. Immunotherapy allows the immune system to find and attack #hidden cancer cells, helping cancer patients live longer lives. However, many patients get little or no benefit from these revolutionary #treatments. Immune #checkpoint #inhibitors are the most used immunotherapies. They work by recognizing and blocking proteins that cancer cells use to hide from the immune system. However, cancer cells that don’t have these proteins use different ways to hide. Since patients with these cancers don’t respond to immune checkpoint inhibitors, researchers are keen to develop new #immunotherapies with different #targets. ➡ 💎 You can find more pieces of work by clicking here. https://lnkd.in/eSG67K5G #tetracycline #antibiotics #T_lymphocytes #immune #system #cancer #galactin_1 #protein #cancer_cells #suppresses #immune_system #immunotherapies