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

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

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 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

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

Novel immune checkpoint target discovered by Dr. Lieping Chen's group👏: The researchers investigated mechanisms associated with T cell exclusion using a genome-wide screen of >1000 soluble human proteins in chemokine-mediated T cell migration. Phospholipase A2 group 10 (PLA2G10) was identified as a candidate and is highly expressed in several human cancers. Overexpression of PLA2G10 in immunologically hot murine tumor lines prevented T-cell infiltration and responsiveness to anti–PD–1 therapy. Abstract: T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell–recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti–PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10’s enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy. SCIENCE IMMUNOLOGY 26 Apr 2024 https://lnkd.in/eKMpsQhr

🧬 Personalized Cancer Vaccines: A New Hope in the Fight Against Cancer 🧬 Exciting news in the world of cancer treatment! Scientists are developing personalized cancer vaccines that train the immune system to recognize and destroy a patient's unique tumor mutations, known as neoantigens. This breakthrough could revolutionize how we treat cancer. 🔍 Key Highlights: -Targeted Treatment: Unlike preventive vaccines, personalized cancer vaccines aim to eliminate leftover cancer cells after treatments like surgery or chemotherapy, reducing the risk of recurrence. - Recent Advancements: Moderna's mRNA-based vaccine, successful against melanoma, is now showing promising results in treating HPV-negative head and neck cancer. In trials, 14 participants saw tumor control, with two experiencing complete remission. - Innovative Solutions: Transgene's TG4050 vaccine, combined with surgery and traditional therapies, resulted in no cancer recurrences in a group of head and neck cancer patients after over a year of follow-up. - Broader Impact: BioNTech and Genentech's personalized vaccine targeting pancreatic cancer showed strong immune responses and lower recurrence rates in patients, with a larger phase 2 trial underway. 💡 Why It Matters: These early-stage studies offer hope and highlight the potential of personalized cancer vaccines to transform cancer treatment. By targeting unique tumor mutations, these vaccines could provide more effective and tailored therapies for patients. Let's stay hopeful and support the incredible advancements in cancer research! 🌟💪 #CancerResearch #PersonalizedMedicine #Immunotherapy #HealthcareInnovation #CancerTreatment #MedicalBreakthroughs #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

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 

🔬 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: