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Sleeping Threats: Immune System’s Watch on Dormant Cancer
Curator: Dr. Sudipta Saha, Ph. D.
The immune system’s role in regulating dormant cancer cells has been increasingly elucidated, revealing a complex interplay that influences metastasis and cancer recurrence. Dormant cells, which enter a non-proliferative state, can evade immune detection and remain quiescent for prolonged periods.
Mechanisms of immune evasion include down-regulation of antigen presentation and residence within immune-privileged niches such as bone marrow. Both innate and adaptive immunity, particularly CD8+ T cells and natural killer cells, are involved in maintaining dormancy and preventing metastatic outgrowth.
Micro-environmental factors that modulate immune surveillance and dormancy status have been identified. Changes in cytokine profiles and inflammation can disrupt dormancy, leading to cancer cell reactivation and metastasis.
Therapeutic approaches to sustain dormancy or eliminate dormant cells are under development. These include immune checkpoint inhibitors, cancer vaccines, and cytokine modulators aimed at enhancing immune recognition and clearance.
By targeting dormant cancer cells through immune modulation, it is anticipated that metastasis can be delayed or prevented, significantly improving long-term patient outcomes and reducing cancer mortality.
Cancer Surgery Rethought: Immunotherapy Takes the Lead
Curator: Dr. Sudipta Saha, Ph.D.
In a recent phase 2 study published in The New England Journal of Medicine, the efficacy of nonoperative management was assessed in patients with mismatch repair–deficient (dMMR) solid tumors. Instead of undergoing curative-intent surgery, patients with stage I to III dMMR tumors were administered immune checkpoint inhibitors.
The study was conducted across two cohorts involving 117 patients. After two years of follow-up, a recurrence-free survival rate of 92% (95% CI, 86 to 99) was achieved. It was found that complete clinical responses could be maintained without surgical intervention, and substantial preservation of organ function was observed.
The avoidance of surgery was associated with fewer treatment-related complications and a significant improvement in patients’ quality of life. It has been emphasized that dMMR tumors, being highly immunogenic, respond exceptionally well to immune checkpoint blockade, thereby offering a viable alternative to conventional surgery-based treatment plans.
While the study’s findings have been considered ground breaking, long-term data have been recommended to fully validate this approach. Future studies are expected to refine patient selection criteria and monitoring strategies to ensure sustained outcomes.
Overall, a potential shift in the standard of care for patients with early-stage dMMR tumors has been proposed, highlighting how personalized immunotherapy can redefine oncological practice.
Resitu Medical Sets Stage for Breakthrough in Breast Tumour Removal
Curator: Dr. Sudipta Saha, Ph.D.
Resitu Medical, a Swedish company specializing in minimally invasive breast tumour removal, has announced the appointment of Stefan Sowa as its new Chief Executive Officer. Strategic leadership is being strengthened as the company moves towards commercialization in both European and American markets.
A novel electrosurgical device, designed to excise entire breast lesions during the biopsy procedure, is being developed by Resitu. The device is intended to minimize the need for open surgery by allowing intact removal of tissue with minimal bleeding, guided by real-time ultrasound imaging. Preclinical studies are currently being conducted, and preparations for FDA clearance and CE marking are underway.
ISO 13485 certification for the design, development, manufacturing, and sales of the device has been successfully obtained. Investment has been secured from major shareholders, including Novoaim, ALMI Invest Stockholm, and STOAF, to support the finalization of the product and the initiation of serial production for clinical trials.
Through the use of its technology, false negatives are hoped to be reduced, while patient outcomes and diagnostic accuracy are expected to be significantly improved. The burden on healthcare systems may also be alleviated by minimizing the need for recalls and secondary biopsies.
Positive attention has been garnered at major medical conferences, with workshops hosted at events such as the Uppsala Breast Meeting, and favourable media coverage has been achieved. With Stefan Sowa at the helm, Resitu’s innovative device is poised to transform breast cancer management practices globally.
Powerful Cancer-Fighting Foods and Their Role in Body Repair
Curator: Dr. Sudipta Saha, Ph.D.
In the search for dietary approaches to prevent and fight cancer, certain foods have been found to possess potent anti-cancer properties. These foods not only help reduce the risk of cancer but also assist in repairing the body. Five such foods are green tea, broccoli like vetables, papaya, purple potatoes, and pomegranate—and the bioactive compounds responsible for their benefits.
1. Green Tea
Green tea, particularly rich in the catechin epigallocatechin gallate (EGCG), has gained considerable attention for its cancer-fighting properties. EGCG functions as a potent antioxidant, neutralizing free radicals and reducing oxidative stress, which is a key factor in the development of cancer. Studies suggest that EGCG can inhibit cancer cell proliferation by disrupting the signaling pathways essential for cell growth and survival, especially in breast, prostate, and colorectal cancers. Additionally, green tea has been shown to enhance the body’s immune function, making it more effective at targeting abnormal cells. EGCG induces apoptosis (programmed cell death) in cancer cells, halts angiogenesis (the formation of new blood vessels that nourish tumors), and inhibits metastasis (the spread of cancer cells to other parts of the body).
2. Broccoli and Cauliflower
Cruciferous vegetables like broccoli and cauliflower are rich in sulforaphane, a compound known for its detoxifying and anti-carcinogenic properties. Sulforaphane activates the body’s natural detoxification enzymes, which help eliminate carcinogens before they can damage cells. Moreover, it has been shown to inhibit the growth of various cancer cells, including those of the colon, breast, and prostate. Sulforaphane enhances the activity of phase II detoxification enzymes and induces apoptosis in cancer cells. It also inhibits histone deacetylase, an enzyme associated with cancer cell growth, thus preventing cancerous cells from replicating.
3. Papaya
Papaya is rich in carotenoids such as beta-carotene, lycopene, and beta-cryptoxanthin, which are powerful antioxidants. These compounds neutralize free radicals, reducing oxidative stress that can lead to cancer. Lycopene, in particular, has been linked to a lower risk of cancers, including those of the prostate, breast, and lung. Papaya also contains other bioactive compounds that help modulate immune responses, supporting the body’s ability to identify and destroy cancer cells. Carotenoids act by scavenging free radicals and reducing oxidative stress. Lycopene has also been shown to regulate cell cycle progression and inhibit growth factor signaling in cancer cells.
4. Purple Potatoes
Purple potatoes are unique due to their high levels of anthocyanins, which not only provide them with their distinctive color but also contribute to cancer prevention. Studies suggest that anthocyanins in purple potatoes help repair damaged tissues by promoting stem cell regeneration. They also have anti-inflammatory and anti-proliferative effects, which are crucial for halting cancer growth. Anthocyanins inhibit the growth of cancer cells by inducing cell cycle arrest and promoting the repair of damaged tissues through stem cell activation.
5. Pomegranate
Pomegranates are rich in ellagitannins, compounds that break down into ellagic acid in the body. Ellagic acid has been shown to possess anti-cancer properties by inhibiting tumor growth and promoting apoptosis in cancer cells. Pomegranate juice has demonstrated potential in reducing the progression of cancers such as breast and prostate cancer, due to its ability to suppress inflammation and oxidative stress. Ellagitannins and their metabolites inhibit cell proliferation and induce apoptosis. They also act by reducing inflammation and inhibiting the pathways involved in cancer cell survival and growth.
Conclusion
Incorporating foods like green tea, broccoli, papaya, purple potatoes, and pomegranates into your diet may help fight cancer and promote the repair of damaged tissues. The bioactive compounds found in these foods—EGCG, sulforaphane, carotenoids, anthocyanins, and ellagitannins—work through various mechanisms to inhibit cancer cell growth, induce apoptosis, and support the body’s natural repair processes. Including these nutrient-dense foods in your diet may contribute to overall health and resilience against cancer.
Armored CD7-CAR T Cells: A Fratricide-Resistant Solution for T-ALL Therapy
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
This research reported in Nature Medicine addresses the challenge of treating T-cell acute lymphoblastic leukemia (T-ALL) with CAR T-cell therapy, particularly focusing on CD7, a surface marker highly expressed on T-ALL cells. The authors develop a novel CAR T-cell therapy that targets CD7, but with a crucial innovation which is fratricide resistance.
Fratricide, a phenomenon where CAR T cells kill each other (killing sister cells) due to shared CD7 expression, has been a significant problem in using CD7-directed therapies. To overcome this, the researchers made CD7-negative CAR T cells (CD7-CAR T cells) by knocking out CD7 from the CAR T cells themselves, preventing them from attacking one another.
Their preclinical results show that these CD7-CAR T cells exhibit strong anti-leukemic activity in T-ALL models, both in vitro and in vivo.
The fratricide-resistant T cells not only maintain their potency but also display enhanced proliferation and persistence, crucial for sustained therapeutic effects. Additionally,
the study highlights the feasibility and safety of this approach by demonstrating no adverse off-target effects or side effects, making it a potentially promising treatment for T-ALL patients who have limited options.
The research presents a significant advancement in CAR T-cell therapy by addressing the challenge of fratricide, offering a new, effective, and safe therapeutic option for T-ALL patients. The development of fratricide-resistant CD7-CAR T cells could lead to more successful outcomes in clinical applications, revolutionizing the treatment for T-ALL patients.
Reporter: Danielle Smolyar, Research Assistant 3 – Text Analysis for 2.0 LPBI Group’s TNS #1 – 2020/2021 Academic Internship in Medical Test Analysis (MTA)
Recently, researchers have found many ways to manipulate and alter gene activity in specific cells. As a result of seeing this alteration, it has caused much development and progress in understanding cancer, brain function, and immunity.
IMAGE SOURCE: 3D-model of DNA. Credit: Michael Ströck/Wikimedia/ GNU Free Documentation Lic
Tissues and Organs are composed of cells that look the same but have different roles. For example, single-cell analysis allows us to research and test the cells within an organ or cancerous tumor. However, the single-cell study has its boundaries and limits in trying a more significant number of cells. This result is not an accurate data and analysis of the cells.
Mulqueen, R. M., Pokholok, D., O’Connell, B. L., Thornton, C. A., Zhang, F., O’Roak, B. J., Link, J., Yardımcı, G. G., Sears, R. C., Steemers, F. J., & Adey, A. C. (2021, July 5). High-content single-cell combinatorial indexing. Nature News. https://www.nature.com/articles/s41587-021-00962-z
states that the new method gives us the ability to have a ten-fold improvement in the amount of DNA produced from a single DNA sequence. A DNA sequence is composed of units which are called bases. The sequence puts the bases in chronological order for it to code correctly.
To understand cancer better, single-cell studies are a crucial factor in doing so. Different cells catch on to other mutations in the DNA sequence in a cancerous tumor, which ultimately alters the DNA sequence. This results in tumor cells with new alterations, which could eventually spread to the rest of the body.
Adey and his team provided evidence that the method they had created can show DNA alterations that have come from cells present in tumor samples from patients with pancreatic cancer. Adey stated,
quote “For example, you can potentially identify rare cell subtypes within a tumor that are resistant to therapy.”
Abey and his team have been working with OHSU Knight Cancer Institute, and with them, they are testing a single-cell method to see if patients’ tumors have changed by doing chemo or drug therapy.
This new method allows itself to create DNA libraries and fragments of DNA that helps analyze the different genes and mutations within the sequence. This method uses something called an enzymatic reaction that attaches primers to the end of each DNA fragment. For the cells to be analyzed, each primer must be present on both ends of the fragment.
As a result of this new method, all library fragments present must-have primers on both ends of the fragments. At the same time, it improves efficiency by reducing its sequencing price overall, that these adapters can be used instead of the regular custom workflows.
4.1.2 The race to map the human body — one cell at a time, A host of detailed cell atlases could revolutionize understanding of cancer and other diseases
4.1.3 Single-cell Genomics: Directions in Computational and Systems Biology – Contributions of Prof. Aviv Regev @Broad Institute of MIT and Harvard, Cochair, the Human Cell Atlas Organizing Committee with Sarah Teichmann of the Wellcome Trust Sanger Institute
4.1.7 Norwich Single-Cell Symposium 2019, Earlham Institute, single-cell genomics technologies and their application in microbial, plant, animal and human health and disease, October 16-17, 2019, 10AM-5PM
4.2.1 How to build a human cell atlas – Aviv Regev is a maven of hard-core biological analyses. Now she is part of an effort to map every cell in the human body.
4.2.2 Featuring Computational and Systems Biology Program at Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute (SKI), The Dana Pe’er Lab
4.3.2 eProceedings 2019 Koch Institute Symposium – 18th Annual Cancer Research Symposium – Machine Learning and Cancer, June 14, 2019, 8:00 AM-5:00 PM ET MIT Kresge Auditorium, 48 Massachusetts Ave, Cambridge, MA
4.4.1 iBioChips integrate diagnostic assays and cellular engineering into miniaturized chips that achieve cutting-edge sensitivity and high-throughput. We have resolved traditional biotech challenges with innovative biochip approaches
4.4.2 Targeted Single-Cell Solutions for High Impact Applications – Mission Bio’s Tapestri® Platform is the only technology that provides single-cell targeted DNA sequencing at single-base resolution.
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