Takashi Suzuki’s Post

Very promising approach to cancer immunotherapy

The use of #engineeredviruses in #cancertreatment is gaining significant traction, offering new avenues for enhancing immune responses against #tumor cells. We had an insightful interview with Aino Kalervo, Chief Operating Officer at TILT Biotherapeutics Ltd, where she shared how their engineered #oncolytic #adenovirus, #TILT123, is genetically modified to selectively attack #cancer cells while preserving healthy tissue.  Discussing results from ongoing clinical trials, particularly in #ovariancancer, Aino Kalervo, underscored the potential of TILT-123 to transform cold tumors into immune-responsive sites #immunotherapy https://lnkd.in/dearawez

Our research provides crucial insights into pancreatic ductal adenocarcinoma (PDAC). Hypoxia, a defining characteristic of PDAC, correlates with disease severity, influencing treatment response, invasiveness, and immunosuppression. Utilizing the Buffa gene signature, we pinpointed LGALS3 as a pivotal gene linked to high hypoxia levels. Elevated hypoxia is associated with reduced levels of T cells, NK cells, and dendritic cells, along with increased immunosuppressive molecules. These findings propose innovative strategies for advancing PDAC immunotherapy by targeting both hypoxia and specific immune elements. Kudos to the team's exceptional work, particularly acknowledging Hassan Sadozai's contributions. https://lnkd.in/es9rQuXv #pancreaticcancer #immunology #immunotherapy #teamcollaboration #teameffort #cancertreatment #cancerresearch #medicaladvancements #transcriptomics #collaborations #interdisciplinary #leadership #leadershipdevelopment #machinelearning

Genetically modified T cell immunotherapies have shown impressive results in treating B cell acute lymphoblastic leukemia by using a patient's own T cells to attack cancer. These methods also hold promise for treating a wide range of other conditions, including various cancers, infectious diseases, and autoimmune disorders. This is achieved by inserting a transgenic T cell receptor or a chimeric antigen receptor into T cells, allowing them to specifically target and destroy cancer cells. However, early research indicates a need for the development of more sophisticated genetic controls over these engineered T cells to maximize their safety and effectiveness. In this review, authors discuss how advancements in genetics and genome engineering are paving the way for the next wave of adoptive T cell therapies. https://lnkd.in/e2-YAZsM

Zhang, D., Wang, M., Ma, S. et al. Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages. Cancer Gene Ther (2024). https://lnkd.in/dAiqxzsJ "Abstract Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC."

Multiple genetic loci are associated with lung cancer risk, but the underlying genetic mechanisms remain poorly understood. Dr. Erping Long and colleagues performed single-cell RNA-seq and ATAC-seq analyses of lung cells from ever- and never-smokers; they report candidate cis-regulatory elements overlapping with candidate causal variants in lung cancer risk loci and potential susceptibility genes. Authors include: Jiyeon Choi, Jinhu Yin, Alex Kane, Harsh Patel, PhD, Thong Luong, Tongwu Zhang, Wei Zhao, Qing (NIH/NCI) Lan, Jianxin Shi https://lnkd.in/e5uqvr7H

Cancers exploit coinhibitory receptors on T cells to escape tumor immunity, and targeting such mechanisms has shown remarkable clinical benefit, but in a limited subset of patients. We hypothesized that cancer cells mimic noncanonical mechanisms of early development such as axon guidance pathways to evade T cell immunity. Using gain-of-function genetic screens, we profiled axon guidance proteins on human T cells and their cognate ligands and identified fibronectin leucine-rich transmembrane protein 3 (FLRT3) as a ligand that inhibits T cell activity. We demonstrated that FLRT3 inhibits T cells through UNC5B, an axon guidance receptor that is up-regulated on activated human T cells. FLRT3 expressed in human cancers favored tumor growth and inhibited CAR-T and BiTE + T cell killing and infiltration in humanized cancer models. https://lnkd.in/e7h_2R33

Did you know that only 15% of lifelong smokers develop lung cancer, and a significant number of cases occur in never-smokers? This suggests that inherited genetic factors play a crucial role in the disease. A recent review highlights the importance of germline testing in lung cancer patients, which can: - Identify individuals at risk - Inform tailored therapeutic approaches - Enable successful prevention through genetic counseling and screening The incorporation of next-generation sequencing in clinical practice has led to the identification of cancer-predisposing mutations in a growing number of patients. Let's continue to advance our understanding of lung cancer and improve patient outcomes through personalized medicine! #LungCancer #GermlineTesting #PersonalizedMedicine https://lnkd.in/g5c5uQHQ

My work in 2010 shares similarities with this research approach. We utilized similar techniques to analyze immune cell heterogeneity and identify distinct immunotypes based on gene expression profiles. This work underscores the continued importance and potential of immunoprofiling in advancing cancer treatment strategies. #immunoprofiling #cancerresearch #geneprofiling #immunotypes #biotech #oncology

Collab🚨: CRI's McBrayer Lab contributed to a discovery published in Science Magazine from the Manguso Lab & Bardeesy Lab at Mass General Hospital Cancer Center that defines a new #cancer-causing mechanism associated with IDH1 mutations (the most commonly mutated metabolic gene across cancers). From Sam McBrayer, Ph.D.: "They found that IDH1 mutations repress expression and sensing of transposable viral elements in the genome that can trigger innate immune signaling in brain and liver cancers. "Drugs that inhibit IDH1 mutant enzymes can reverse this process, leading to anti-tumor immune responses. These findings provide new insights into how IDH1 mutations, as well as drugs that target these mutations, regulate cancer growth." Read it here: https://lnkd.in/gheTrga8 #relentlessdiscovery #CancerResearch