Easy IMMUNO-ATMPs’ Post

One of the most exciting developments in recent years is using engineered immune cells, called CAR T cells, to fight cancer. These cells are modified to recognize and destroy cancer cells and have shown remarkable results in some blood cancers. But what if we could make these cells even more powerful and versatile? A new study published in Nature by Roybal, Choi and their team has done just that, by borrowing a mutation from cancer cells themselves. This mutation, called CARD11–PIK3R3, enhances the function and survival of CAR T cells, allowing them to infiltrate and eliminate solid tumors that are usually resistant to current therapies. This is a game-changing approach that could open the door for better CAR T cell therapies in the future. Imagine being able to treat cancers such as breast, lung, or skin cancer with a simple infusion of your own immune cells, supercharged with a cancer mutation. Sounds like science fiction, right? Well, not quite. There are still some challenges and risks that need to be addressed before this approach can be used in humans. For one thing, we need to make sure that these mutated cells do not become cancerous themselves, or cause unwanted side effects such as inflammation or autoimmunity. We also need to test their safety and efficacy in larger and more diverse animal models, and eventually in clinical trials. https://lnkd.in/dMTJ_298

https://lnkd.in/drihYQGa "Highlights • 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 Summary Total tumor clearance through immunotherapy is associated with a fully coordinated innate and adaptive immune response, but knowledge on the exact contribution of each immune cell subset is limited. We show that therapy-induced intratumoral CD8+ T cells recruited and skewed late-stage activated M1-like macrophages, which were critical for effective tumor control in two different murine models of cancer immunotherapy. The activated CD8+ T cells summon these macrophages into the tumor and their close vicinity via CCR5 signaling. Exposure of non-polarized macrophages to activated T cell supernatant and tumor lysate recapitulates the late-stage activated and tumoricidal phenotype in vitro. The transcriptomic signature of these macrophages is also detected in a similar macrophage population present in human tumors and coincides with clinical response to immune checkpoint inhibitors. The requirement of a functional co-operation between CD8+ T cells and effector macrophages for effective immunotherapy gives warning to combinations with broad macrophage-targeting strategies."

📃Scientific paper: TBX3 promotes the epithelial mesenchymal transition of cervical cancer by upregulating ID1 Abstract: In this study, we aim to investigate the role and mechanism of T-box transcription factor 3 (TBX3) in cervical cancer. The mRNA and protein expression of TBX3, inhibitor of DNA binding 1 (ID1), and epithelial mesenchymal transition (EMT) markers (E-Cadherin, N-Cadherin, and vimentin) were measured using qRT-PCR and Western blot. shTBX3 and shID1 were transfected into SiHa cells to knockdown TBX3 and ID1. The metastasis and invasion abilities of cervical cancer cells were determined using a wound healing assay and an invasive assay. The shTBX3- and shID1-transfected SiHa cells were injected into nude mice using a xenograft tumor growth model. We found that TBX3 and ID1 were highly expressed in cervical cancer cells. Importantly, silencing TBX3 and ID1 significantly reduced the migration and metastasis of cervical cancer cells. In addition, silencing TBX3 and ID1 significantly inhibited the EMT, evidenced by the increased E-cadherin, and decreased N-cadherin and vimentin. The size and weight of the xenograft tumor were significantly reduced by shTBX3 and shID1. We demonstrate that TBX3 or ID1 knockdown can effectively inhibit cervical cancer cells migration and invasion. These findings indicate that TBX3 and ID1 can act as potential therapeutic targets for the prevention and treatment of cervical cancer. Continued on ES/IODE ➡️ https://etcse.fr/BCGy6 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

💥 Another live cell image video showing a NK cell inducing cell death. I'm not 100% sure, but this might be all apoptosis? According to my references Natural Killer (NK) cells can induce apoptosis in target cells via two main mechanisms: 1) They can release cytotoxic granules containing perforin and granzymes. Perforin induces pores in the target cell membrane, allowing granzymes to enter and trigger cell death. An apoptotic cascade. 2) NK cells engage via TNFR - tumor necrosis factor receptors - such as Fas on the target cell's surface. This interaction activates the caspase pathway, leading to programmed cell death. Both mechanisms ensure rapid and targeted elimination of infected or abnormal cells. 🧬 Do we see both here? #apoptosis #immunology

"In the trial, we show that the expansion strategy for immune cells that can fight Merkel cell cancer is relevant for people with this type of cancer. We have designed some molecular structures that contain a number of different molecules that can activate the reaction in the immune system that can defeat the cancer cells," Sine Reker Hadrup explains. A new immunotherapy treatment for the aggressive skin cancer, Merkel cell carcinoma, shows great promise in lab experiments. Professor Sine Reker Hadrup has headed an international team, who have identified the elements to be conquered to beat this specific type of cancer, and then boosted the patient's immune system to do so. Before a new immunotherapy treatment for patients can be developed, a larger study is needed followed by clinical trials. Read more about this research: https://lnkd.in/dcfR7s3A The results were also recently published in the Journal of Clinical Investigation https://lnkd.in/dtyQx9pK #healthtech #immunotherapy #tcells #cancertreatment

Researchers at City of Hope have discovered that a type of immune cell called human type 2 innate lymphoid cells (ILC2s) can attack and kill various types of cancers, including blood and solid tumors, offering potential for future cancer treatments. 💡In the future, these cells could be manufactured, preserved by freezing and administered to patients. Unlike T cell-based therapies like CAR T cells, which necessitate using the patient's cells due to their specific characteristics, ILC2s might be sourced from healthy donors, presenting a distinct potential therapeutic approach as an allogeneic and 'off-the-shelf' product. Surprisingly, Human ILC2 cells have been found to function as direct cancer killers, unlike their mouse counterparts. Remarkably, something has evolved so distinctly from mouse to human. ➡️ Researchers have developed a method to expand human ILC2 cells from a blood sample and found that these cells can kill tumors, including acute myeloid leukemia, pancreatic cancer, lung cancer, and glioblastoma, through a previously unknown mechanism. ✅ Although there are still many unanswered questions about ILC2s' cancer-killing functions, the team plans to continue their research and explore the broader applications of these findings. The team has successfully overcome the challenge of producing enough ILC2s for clinical trials and has access to facilities that can manufacture these cells in compliance with good manufacturing practices. https://lnkd.in/eas3srtz #cancer #cancerresearch #immunology #immunooncology #precisiononcology #solidtumors #bloodcancer #immunotherapy #targetedtherapy

The groundbreaking research led by Steven A. Rosenberg, M.D., Ph.D., on identifying tumor-targeting T cells in the blood marks a crucial stride in the realm of personalized cancer immunotherapies. Published in Cancer Cell, the study reveals a unique molecular signature for antitumor T cells in blood samples, providing a noninvasive method to obtain these cells for the development of tailored cancer treatments. This discovery is particularly significant for solid tumors, including colorectal, liver, and breast cancers, where customized therapies must recognize individual cancer mutations. The team's ability to isolate and profile gene activity in blood-derived antitumor T cells opens doors to therapeutic applications, suggesting the possibility of amplifying these cells in a lab and reintroducing them to patients. Moreover, the finding that blood-derived T cells show less exhaustion than those inside tumors unveils potential avenues for therapeutic reprogramming. Dr. Rosenberg's work not only expands our understanding of antitumor immunity but also lays a foundation for advancing targeted cancer therapies through noninvasive means.

Happy Monday all! Check out this open access Cancer Cell review by Karin E. de Visser and Johanna A. Joyce, "The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth." Summary: Cancers represent complex ecosystems comprising tumor cells and a multitude of non-cancerous cells, embedded in an altered extracellular matrix. The tumor microenvironment (TME) includes diverse immune cell types, cancer-associated fibroblasts, endothelial cells, pericytes, and various additional tissue-resident cell types. These host cells were once considered bystanders of tumorigenesis but are now known to play critical roles in the pathogenesis of cancer. The cellular composition and functional state of the TME can differ extensively depending on the organ in which the tumor arises, the intrinsic features of cancer cells, the tumor stage, and patient characteristics. Here, we review the importance of the TME in each stage of cancer progression, from tumor initiation, progression, invasion, and intravasation to metastatic dissemination and outgrowth. Understanding the complex interplay between tumor cell-intrinsic, cell-extrinsic, and systemic mediators of disease progression is critical for the rational development of effective anti-cancer treatments. #drugdiscovery #tme #tumors #cancerresearch #immunotherapy #immunooncology #scientificresearch

Great potential for cell therapy might one day be revealed in these cells. Check this review to see how far the research front has progressed! Abstract The premise of cancer immunotherapy is that cancers are specifically visible to an immune system tolerized to healthy self. The promise of cancer immunotherapy is that immune effector mechanisms and immunological memory can jointly eradicate cancers and inoperable metastases and de facto vaccinate against recurrence. For some patients with hitherto incurable diseases, including metastatic melanoma, this promise is being realized by game-changing immunotherapies based on αβ T cells. Today’s challenges are to bring benefit to greater numbers of patients of diverse ethnicities, target more cancer types, and achieve a cure while incurring fewer adverse events. In meeting those challenges, specific benefits may be offered by γδ T cells, which compose a second T cell lineage with distinct recognition capabilities and functional traits that bridge innate and adaptive immunity. γδ T cell–based clinical trials, including off-the-shelf adoptive cell therapy and agonist antibodies, are yielding promising results, although identifiable problems remain. In addressing those problems, we advocate that immunotherapies be guided by the distinctive……...

NK and cancer cells via apoptosis and necrosis