Cancer Research Institute (CRI)’s Post

In a study funded by the Pediatric Immunotherapy Network (PIN) & Informatics Technology for Cancer Research (ITCR) program, Bjoern Peters, Stephen P. Schoenberger, et al. developed a platform combining bioinformatic analysis with functional immunology to identify neoantigen-specific T cells in patients with cancer. This approach can be used to identify and validate clinically actionable neoantigens. When discussing the research, Dr. Bjoern Peters (a co-lead author of the study) said "Every cancer patient is different, but this research is an important step toward finding immune cell targets relevant for individual patient tumors. https://lnkd.in/ghG4XE37

I like this study very much, smart and elegant. However, there is a big issue. At the beginning of the Results, it stated, "To evaluate the feasibility of cDC1 reprogramming in situ as a cancer immunotherapeutic modality, we first assessed whether the PIB transcription factors were sufficient to drive in vivo reprogramming of tumor cells to immunogenic cDC1-like cells within the TME without relying on artificial antigens or exogenous stimulation, and then characterized the induced immune mechanisms. " In this study, the LV vector used to make cDC1 reprogram encoded PIB followed by IRES-eGFP. eGFP is well known for its immunogenicity (https://lnkd.in/dYEXsdim). I suspected that all the tumor responses shown in this study relied on eGFP, an artificial antigen. https://lnkd.in/eTQuYD4X

#researchmatters 🚨 New breakthrough in cancer research! Researchers from the University of Pittsburgh and UPMC Hillman Cancer Center have discovered that depriving tired T-cells of lactic acid helps them regain their cancer-fighting zeal. This innovative finding opens up new possibilities for enhancing T-cell therapy in cancer treatment. Learn more here: https://lnkd.in/gy5MKeBa At Cyagen, we support this cutting-edge research with our diverse range of Immuno-Oncology Mouse Models. Our humanized models enable researchers to study immune responses in a human-like environment, improving the development of cancer immunotherapies. Explore how Cyagen's models can help accelerate your cancer research and enhance your studies in immune modulation: https://lnkd.in/gNm_9XYe #CancerResearch #Immunotherapy #TCells #Oncology #Biotech #MedicalResearch #Innovation #Cyagen

CHEMOTHERAPY IS A DOUBLE-EDGED SWORD NEW FINDINGS MIGHT IMPROVE OUTCOMES When cancer cells die, they release their contents, including tumor-specific antigens that can be targeted by the immune system. While it has long been thought that tumor cell death is an important up-regulator of tumor immunity, recent research shows that the process of cell death called necroptosis is a double-edged sword, as it results in the release of a cytokine called interleukin-1α that dampens immunity by recruiting immunosuppressive myeloid cells into the tumor bed. As a consequence, chemotherapeutic agents, cellular toxins that kill large numbers of cancer cells (and bystander cells) by necroptosis, generate an immunosuppressive response that dampens host immunity. As in all things related to cancer, the underlying biology is always more complicated than you think at first site. In animal models, treatment with an antibody to block the activity of interleukin-1α improved chemotherapeutic outcomes. It remains to be seen if this observation translates into human patients, as we have cured far more rodents or cancer than human patients. We can say that theoretically, it certainly looks promising! #cancer #cancerresearch #cancertreatment #cancerawareness #oncology #medicine #biochemistry #breastcancerawareness #Melanoma #lungcancer #immunotherapy #genetics #biotechnologypharmaprofessionals #cellbiology #tumorimmunology

By examining antigen architectures, MIT researchers built a therapeutic cancer vaccine that may improve tumor response to immune checkpoint blockade treatments. | Click below to read the full article on Sunalei

"Highlights • DT10 is superior, visually interpretable, and applicable in varied clinical settings • Gene subtype and co-mutation analysis enhances individualized treatment precision • Large datasets (>3,000 patients) anchor robust predictive efficacy of biomarkers • TME data provide biological evidence supporting predictions of the DT10 model Summary Background Predictive biomarkers and models of immune checkpoint inhibitors (ICIs) have been extensively studied in non-small cell lung cancer (NSCLC). However, evidence for many biomarkers remains inconclusive, and the opaqueness of machine learning models hinders practicality. We aimed to provide compelling evidence for biomarkers and develop a transparent decision tree model. Methods We consolidated data from 3,288 ICI-treated patients with NSCLC across real-world multicenter, public cohorts and the Choice-01 trial (ClinicalTrials.gov: NCT03856411). Over 50 features were examined for predicting durable clinical benefits (DCBs) from ICIs. Noteworthy biomarkers were identified to establish a decision tree model. Additionally, we explored the tumor microenvironment and peripheral CD8+ programmed death-1 (PD-1)+ T cell receptor (TCR) profiles. Findings Multivariate logistic regression analysis identified tumor histology, PD-ligand 1 (PD-L1) expression, tumor mutational burden, line, and regimen of ICI treatment as significant factors. Mutation subtypes of EGFR, KRAS, KEAP1, STK11, and disruptive TP53 mutations were associated with DCB. The decision tree (DT10) model, using the ten clinicopathological and genomic markers, showed superior performance in predicting DCB in the training set (area under the curve [AUC] = 0.82) and consistently outperformed other models in test sets. DT10-predicted-DCB patients manifested longer survival, an enriched inflamed tumor immune phenotype (67%), and higher peripheral TCR diversity, whereas the DT10-predicted-NDB (non-durable benefit) group showed an enriched desert immune phenotype (86%) and higher peripheral TCR clonality."

“The CNIO group has identified a key molecule in the process, called TIMP1. "Pro-tumor astrocytes produce TIMP1, and this protein is involved in disabling the defensive cells that should kill cancer cells," says Priego. Having demonstrated that this molecule, TIMP1, acts on immune system cells and renders them less effective, the CNIO team proposes to use it as a biomarker to detect brain metastases affected by this immunosuppressive mechanism. "TIMP1 is a good biomarker, because it is secreted in significantly higher amounts in the cerebrospinal fluid of patients with brain metastases," says Priego. #brainmetastasis #immunotherapy #braincancer #cancerresearch #bloodbrainbarrier

#cancerresearch #oncology #cancertreatment #immunology https://lnkd.in/gkaE_ht2 Abstract Most #metastatic #cancers remain incurable due to the emergence of apoptosis-resistant clones, fuelled by #intratumour #heterogeneity and tumour evolution. To improve treatment, therapies should not only kill cancer cells but also activate the immune system against the tumour to eliminate any residual cancer cells that survive treatment. While current cancer therapies rely heavily on apoptosis — a largely immunologically silent form of cell death — there is growing interest in harnessing immunogenic forms of cell death such as necroptosis. Unlike #apoptosis, #necroptosis generates second messengers that act on immune cells in the tumour microenvironment, alerting them of danger. This lytic form of cell death optimizes the provision of antigens and adjuvanticity for immune cells, potentially boosting anticancer treatment approaches by combining cellular suicide and immune response approaches. In this Review, we discuss the mechanisms of necroptosis and how it activates antigen-presenting cells, drives cross-priming of CD8+ T cells and induces antitumour immune responses. We also examine the opportunities and potential drawbacks of such strategies for exposing cancer cells to immunological attacks.

Immune checkpoint inhibitors (ICIs) are a type of drug used to regulate the immune response and help T cells identify tumor cells in certain cancer patients. There are currently limited noninvasive options for monitoring ICI treatment and predicting which patients will benefit the most from this form of #immunotherapy. In a 2023 study, Dr. Weijie Ma et al. developed a method of spectral #flowcytometry to identify potential immune biomarkers for ICI treatment in blood samples from lung cancer patients. Check out the paper to learn how spectral flow, a relatively new method of cytometry, has the potential to be a powerful clinical tool in #oncology. Collaborators: Bridget McLaughlin, Cytek Biosciences, Varun Viswanath, Jeremy Chien, Qianjun Zhang, Jonathan Van Dyke https://lnkd.in/eVeDjPbi 

🌟 Exciting Findings in NSCLC Research! 🌟SeekOne® DD Single Cell 5' Transcriptome-seq was utilized to investigate the macrophage landscape of non-small cell lung cancer (NSCLC) tissues. 🔎𝗙𝗶𝗻𝗱𝗶𝗻𝗴𝘀: This study revealed the existence of distinct macrophage subpopulations and differentiation trajectories within the tumor microenvironment. Notably, researchers discovered that tumor cells secrete CXCL8, which activates purine metabolism and related signaling pathways, promoting an immunosuppressive phenotype in macrophages. 💡𝗛𝗶𝗴𝗵𝗹𝗶𝗴𝗵𝘁𝘀: By blocking purine metabolism, researchers found the potential to enhance anti-tumor immunity and improve the effectiveness of immunotherapy. 🚀𝗙𝘂𝘁𝘂𝗿𝗲: This groundbreaking research offers a promising new strategy for the treatment of NSCLC, paving the way for future advancements in cancer therapy. https://lnkd.in/gXc3PYh4 #NSCLC #CancerResearch #Immunotherapy #SeekOne #ScientificInnovation #SeekGene #singlecell