May 5, 2017 Stylized illustration of a platelet and T cell. Plus and negative signs are used to symbolically indicate the positive (clotting) and negative (downregulating T cell immunity) effects of platelets. Credit: Emma Vought of the Medical University of South Carolina.
Blood platelets help disguise cancer from the immune system by suppressing T cells, report scientists at the Medical University of South Carolina (MUSC) in the May 5, 2017 issue of Science Immunology. In extensive preclinical tests, a promising T cell therapy more successfully boosted immunity against melanoma when common antiplatelet drugs such as aspirin were added.
Zihai Li, M.D., Ph.D., senior author on the article, is chair of the MUSC Department of Microbiology and Immunology, the program leader for the Cancer Immunology Research Program at MUSC Hollings Cancer Center, and the SmartState Sally Abney Rose Chair in Stem Cell Biology & Therapy. Li studies how tumors hide themselves from the immune system.
Li's team found that platelets release a molecule that suppresses the activity of cancer-fighting T cells. That molecule, unsurprisingly, was TGF-beta, which has been recognized for decades for its role in cancer growth.
Yet this study is the first of its kind. Most TGF-beta is inactive. Li and his group found that the surface of platelets has a protein called GARP, a molecular hook that is uniquely able to trap and activate TGF-beta. Platelets, which are small cell fragments that circulate throughout the blood and are normally involved in clotting, become the major source of activated TGF-beta that invading tumor cells use to suppress T cells. In other words, platelets help give tumors their invisibility cloak from the immune system.
Scientists have known for several years that certain cancers suppress T cells to avoid the immune system. That is why adoptive T cell therapy is one of the most promising advances in modern cancer treatment. It is a type of immunotherapy that awakens the immune system by retraining a patient's T cells to recognize their cancer. T cells are isolated from a patient's blood and retrained, or "primed," to recognize tumor cells. They are then injected back into the patient's bloodstream where they can now hunt and fight cancer.
There was some evidence that platelets might make cancer worse. For example, patients who have excessive clotting related to their cancer almost always have a worse prognosis, according to Li.
"Over the years, it has become appreciated that platelets are doing more than just clotting," says Li.
The first clue that cancer-fighting T cells might be suppressed by the body's own clotting system came when the researchers gave melanoma to mice with genetically defective platelets. Melanoma tumors grew much more slowly and primed T cells were much more active than in mice with normal platelets.
Next, the team isolated platelets and T cells from blood drawn from humans and mice. In both cases, platelets with activated clotting activity suppressed T cell response. It then used mass spectrometry to thoroughly identify the molecules released by activated platelets that most suppressed T cell activity. The molecule with the most T cell suppression was TGF-beta.
Li and his team then studied how platelets activate TGF-beta. In genetically modified mice without GARP, the molecular hook on the surface of platelets, adoptive T cell therapy was more successful at controlling melanoma. This meant that platelets without the ability to grab and activate TGF-beta were not able to suppress cancer-fighting T cells. Similar experiments confirmed this result in mice with colon carcinoma.
Finally, mice with normal platelets that were given melanoma and then adoptive T cell therapy survived longer and relapsed less when aspirin and clopidogrel, two antiplatelet drugs, were added. The researchers noted that antiplatelet drugs by themselves were not successful in combating melanoma in their experiments.
This study could inform future treatment of melanoma and other cancers and offers a sound reason to test antiplatelet drugs in clinical trials of adoptive T cell therapy. In patients with melanoma or other cancers, adoptive T cell therapy may be successful if highly available platelet-blocking drugs such as aspirin are added to the treatment. However, the current standard of care for melanoma is not adoptive T cell therapy, but so-called checkpoint inhibitors.
Li and his group want to know if combination therapy with antiplatelet drugs could improve existing cancer treatment. They are waiting for approval to begin a clinical trial that will test certain checkpoint inhibitors in combination with aspirin and clopidogrel for the treatment of patients with advanced cancers. Li's trial will complement clinical trials that are already testing adoptive T cell therapy as a single treatment for cancer.
"I'm very excited about this," says Li. "We can test simple, over-the-counter antiplatelet agents to really improve immunity and make a difference in how to treat people with cancer."
Explore further: Aspirin slows growth of colon, pancreatic tumor cells
More information: "Platelets subvert T cell immunity against cancer via GARP-TGF axis," Science Immunology (2017). immunology.sciencemag.org/lookup/doi/10.1126/sciimmunol.aai7911
Researchers from Oregon Health and Science University and Oregon State University have found that aspirin may slow the spread of some types of colon and pancreatic cancer cells. The paper is published in the American Journal ...
The molecule CD103 is key to the long-term residence of T cells in the skin and to their anti-tumor function, report a team of researchers at the Medical University of South Carolina (MUSC) and the Dartmouth-Hitchcock Norris ...
Metastasis of cancer cells to sites distant from the primary tumor is the leading cause of cancer-related death, and there is growing evidence that platelets aid the dissemination of cancer cells.
In an article published online ahead of print on March 13, 2017 by the Journal of Clinical Investigation, Medical University of South Carolina (MUSC) investigators report preclinical research showing that moesin, a membrane-domain ...
Scientists at the Medical University of South Carolina (MUSC) have designed an antibody-based therapy that could target the functions of TGF-beta that cause cancer. The therapy targets TGF-beta where it is particularly dangerousdocked ...
After surgery to remove a cancerous tumoreven if the surgery is considered "successful"it's nearly impossible to ensure that all microtumors have been removed from the surgical site. Cancer recurrence is always a major ...
Blood platelets help disguise cancer from the immune system by suppressing T cells, report scientists at the Medical University of South Carolina (MUSC) in the May 5, 2017 issue of Science Immunology. In extensive preclinical ...
A new research study of immune responses to pneumococcal vaccines, commonly given to people with compromised immune systems, young children and people over 65, has identified a type of immune cell which is important in generating ...
Phthalates, which are used as plasticizers in plastics, can considerably increase the risk of allergies among children. This was demonstrated by UFZ researchers in conjunction with scientists from the University of Leipzig ...
The findings have implications for all aspects of medical and scientific research because laboratory mice underpin studies whose results have a transformative effect on human and animal lives through vaccination and other ...
A diet supplemented with soy protein may be an effective adjunct therapy for inflammatory bowel diseases, Penn State researchers reported after completing a study that included mice and cultured human colon cells.
Inside a healthy gut, bacteria and immune cells maintain a delicate balance. If that balance is disturbed, a condition called inflammatory bowel disease or IBD can result. Patients with IBD can experience diarrhea, abdominal ...
Adjust slider to filter visible comments by rank
Display comments: newest first
If you scanned the body for relatively higher TGF concentrations, could you use that information to find active cancers?
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Original post:
Platelets suppress T cell immunity against cancer - Medical Xpress - Medical Xpress
- Close Encounters of Skin and Nerve Cells - The Scientist - April 15th, 2024 [April 15th, 2024]
- OrthoID: Decoding Cellular Conversations with Cutting-Edge Technology - yTech - April 15th, 2024 [April 15th, 2024]
- Impact of aldehydes on DNA damage and aging - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Redefining Cell Biology: Nondestructive Genetic Insights With Raman Spectroscopy - SciTechDaily - March 29th, 2024 [March 29th, 2024]
- Scientists Unravel the Unusual Cell Biology Behind Toxic Algal Blooms - SciTechDaily - March 19th, 2024 [March 19th, 2024]
- Ancient retroviruses played a key role in the evolution of vertebrate brains - EurekAlert - February 21st, 2024 [February 21st, 2024]
- Singapore scientists uncover a crucial link between cholesterol synthesis and cancer progression - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Scientists uncover a way to "hack" neurons' internal clocks to speed up brain cell development - News-Medical.Net - February 4th, 2024 [February 4th, 2024]
- First atomic-scale 'movie' of microtubules under construction, a key process for cell division - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Small RNAs take on the big task of helping skin wounds heal better and faster with minimal scarring - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Shengjie Feng channels the powers of cryogenic electron microscopy - Newswise - January 19th, 2024 [January 19th, 2024]
- Study pinpoints breast cancer cells-of-origi - EurekAlert - January 19th, 2024 [January 19th, 2024]
- New analysis of cancer cells identifies 370 targets for smarter, personalized treatments - News-Medical.Net - January 19th, 2024 [January 19th, 2024]
- EU funding for pioneering research on the treatment of gliomas - EurekAlert - January 19th, 2024 [January 19th, 2024]
- The future of mRNA biology and AI convergence - Drug Target Review - December 22nd, 2023 [December 22nd, 2023]
- The future of artificial breast milk, according to one lab - Quartz - December 22nd, 2023 [December 22nd, 2023]
- Shedding new light on the hidden organization of the cytoplasm - News-Medical.Net - December 22nd, 2023 [December 22nd, 2023]
- Bugs that help bugs: How environmental microbes boost fruit fly reproduction - EurekAlert - December 22nd, 2023 [December 22nd, 2023]
- Cells Move in Groups Differently Than They Do When Alone - NYU Langone Health - December 14th, 2023 [December 14th, 2023]
- Cells move in groups differently than they do when alone - EurekAlert - December 14th, 2023 [December 14th, 2023]
- Seattle Hub for Synthetic Biology plans to transform cells into tiny recording devices - GeekWire - December 14th, 2023 [December 14th, 2023]
- Virginia Tech and Weizmann Institute of Science tackle cell ... - Virginia Tech - October 16th, 2023 [October 16th, 2023]
- Vast diversity of human brain cell types revealed in trove of new ... - Spectrum - Autism Research News - October 16th, 2023 [October 16th, 2023]
- Singamaneni to develop advanced protein imaging method - The ... - Washington University in St. Louis - October 16th, 2023 [October 16th, 2023]
- Researchers find certain cancers can activate 'enhancer' in the ... - University of Toronto - October 16th, 2023 [October 16th, 2023]
- 2023 Hettleman Prizes awarded to five exceptional early-career ... - UNC Research - October 16th, 2023 [October 16th, 2023]
- Faeth Therapeutics Announces National Academy of Medicine ... - BioSpace - October 16th, 2023 [October 16th, 2023]
- From Migrant Farm Worker to Duke Scientist, Everardo Macias ... - Duke University School of Medicine - October 16th, 2023 [October 16th, 2023]
- Finding the golden ticket? Cyclin T1 is required for HIV-1 latency ... - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Spermidine May Improve Egg Health and Fertility - Lifespan.io News - October 16th, 2023 [October 16th, 2023]
- Molecule discovered that grows bigger and stronger muscles - Earth.com - October 16th, 2023 [October 16th, 2023]
- SGIOY: 3 Biotech Stocks With Potential Future Gains - StockNews.com - October 16th, 2023 [October 16th, 2023]
- Association for Molecular Pathology Publishes Best Practice ... - Technology Networks - October 16th, 2023 [October 16th, 2023]
- A new cell type with links to gastric cancer steps up for its mugshot - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Programmed cell death may be 1.8 billion year - EurekAlert - October 16th, 2023 [October 16th, 2023]
- New study confirms presence of flesh-eating and illness-causing ... - Science Daily - October 16th, 2023 [October 16th, 2023]
- New Institute for Immunologic Intervention (3i) at the Hackensack ... - Hackensack Meridian Health - October 16th, 2023 [October 16th, 2023]
- Post-doctoral Fellow in Cancer Biology in the Department of ... - Times Higher Education - October 16th, 2023 [October 16th, 2023]
- Scientists uncover key enzymes involved in bacterial pathogenicity - News-Medical.Net - October 16th, 2023 [October 16th, 2023]
- B cell response after influenza vaccine in young and older adults - EurekAlert - October 16th, 2023 [October 16th, 2023]
- Post-doctoral researcher in yeast cell biology job with UNIVERSITY ... - Times Higher Education - April 8th, 2023 [April 8th, 2023]
- expert reaction to study looking at creating embryo-like structures ... - Science Media Centre - April 8th, 2023 [April 8th, 2023]
- UCF Bone Researcher Receives National Recognition - UCF - April 8th, 2023 [April 8th, 2023]
- PhenomeX to Participate in American Association of Cancer ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Inland Empire stem-cell therapy gets $2.9 million booster - UC Riverside - April 8th, 2023 [April 8th, 2023]
- New finding in roundworms upends classical thinking about animal cell differentiation - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Biology's unsolved chicken-or-egg problem: Where did life come from? - Big Think - April 8th, 2023 [April 8th, 2023]
- Azacitidine in Combination With Trametinib May Be Effective for ... - The ASCO Post - April 8th, 2023 [April 8th, 2023]
- Researchers clear the way for well-rounded view of cellular defects - Phys.org - April 8th, 2023 [April 8th, 2023]
- We were dancing around the lab cellular identity discovery has potential to impact cancer treatments - Newswise - April 8th, 2023 [April 8th, 2023]
- Environmental stressors' effect on gene expression explored in lecture - Environmental Factor Newsletter - April 8th, 2023 [April 8th, 2023]
- RNA therapy restores gene function in monkeys modeling ... - Spectrum - Autism Research News - April 8th, 2023 [April 8th, 2023]
- Traumatic brain injury interferes with immune system cells' recycling ... - Science Daily - April 8th, 2023 [April 8th, 2023]
- Lab-grown fat could give cultured meat real flavor and texture - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Researchers reveal mechanism of polarized cortex assembly in migrating cells - Phys.org - April 8th, 2023 [April 8th, 2023]
- Probing Selfish Centromeres Unveils an Evolutionary Arms Race - The Scientist - April 8th, 2023 [April 8th, 2023]
- Meet the 2023 Outstanding Graduating Students - UMaine News ... - University of Maine - April 8th, 2023 [April 8th, 2023]
- The Worlds Sexiest Fragrance Unveiled, But Its Not For You - Revyuh - April 8th, 2023 [April 8th, 2023]
- City of Hope appoints John D. Carpten, Ph.D., as director of its ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Modernized Algorithm Predicts Drug Targets for SARS-CoV-2, Other ... - GenomeWeb - April 8th, 2023 [April 8th, 2023]
- BU researcher wins $3.9 million NIH grant to develop novel therapeutic modalities for Alzheimer's - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Providing critical insights for animal development - HKU biologists ... - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Students Express Frustrations About the Middle Class Scholarship - The Triton - April 8th, 2023 [April 8th, 2023]
- Mendus redeems the outstanding convertible bonds from Negma ... - GlobeNewswire - April 8th, 2023 [April 8th, 2023]
- Sustainability in research: If you want to green your lab, start with the ... - McGill Reporter - April 8th, 2023 [April 8th, 2023]
- Two-organ chip to answer fatty liver questions - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Blind dating in bacteria evolution - Newswise - April 8th, 2023 [April 8th, 2023]
- White blood cells play unexpected role in clearing out dead liver cells - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Woolly mammoths evolved smaller ears and woolier coats over the 700,000 years that they roamed the Siberian steppes - Newswise - April 8th, 2023 [April 8th, 2023]
- Pathogen mapped: Evolution and potential treatments - Science Daily - March 31st, 2023 [March 31st, 2023]
- ProJenX Announces Formation of Scientific Advisory Board - Yahoo Finance - March 31st, 2023 [March 31st, 2023]
- Science journalist Rebecca Skloot to speak on 'The Immortal Life of ... - Virginia Tech Daily - March 31st, 2023 [March 31st, 2023]
- How cell mechanics influences everything | MIT News ... - MIT News - March 31st, 2023 [March 31st, 2023]
- Artificial Cells The Powerhouse of the Future - SciTechDaily - March 31st, 2023 [March 31st, 2023]
- Basic Science Experts and Information for Media - St. Jude ... - St. Jude Children's Research Hospital - March 31st, 2023 [March 31st, 2023]
- Mendus presents an update on the use of its DCOne platform to source high-quality NK cell therapies at the 8th Annual Innate Killer Summit - Yahoo... - March 31st, 2023 [March 31st, 2023]
- Researchers reveal structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT - Phys.org - March 31st, 2023 [March 31st, 2023]
- Labroots Announces Full Agenda for its 5th Annual Bioprocessing ... - PR Web - March 31st, 2023 [March 31st, 2023]
- RoslinCT and Lykan Bioscience announce that the MHRA has granted an MIA License for their cGMP Manufacturing facilities in Edinburgh, UK - Yahoo... - March 31st, 2023 [March 31st, 2023]
- 'ASBMB opened the doors for me' - ASBMB Today - March 31st, 2023 [March 31st, 2023]