Meet Cyclone: A Monitoring Tool That Watches for Waves of Immune Response

When a patient persistently battles an aggressive cancer, T cells gradually lose their ability to kill. Identifying when T cells exhaust and when to employ additional treatments remains a significant challenge for clinicians. But as patients undergoing long-term treatments or those with advanced cancer often suffer from weakness, it becomes increasingly difficult to obtain samples. So researchers lack longitudinal data on T cell dynamics after administering immunotherapies.

Recently, a team of researchers at the University of Pennsylvania Perelman School of Medicine (Penn Medicine) reported a solution in the form of a novel immunotherapy monitoring tool called Cyclone. Upon testing this tool on immune checkpoint therapeutic regimens, the team discovered that a combination of checkpoint inhibitors triggers large waves of immune response in stage IV melanoma patients. These findings, published in Cancer Cell, provide new insights into drug efficacy and may lead to better treatment monitoring strategies in cancer .

When a patient persistently battles an aggressive cancer, T cells gradually lose their ability to kill. Identifying when T cells exhaust and when to employ additional treatments remains a significant challenge for clinicians. But as patients undergoing long-term treatments or those with advanced cancer often suffer from weakness, it becomes increasingly difficult to obtain samples. So researchers lack longitudinal data on T cell dynamics after administering immunotherapies.

Recently, a team of researchers at the University of Pennsylvania Perelman School of Medicine (Penn Medicine) reported a solution in the form of a novel immunotherapy monitoring tool called Cyclone. Upon testing this tool on immune checkpoint therapeutic regimens, the team discovered that a combination of checkpoint inhibitors triggers large waves of immune response in stage IV melanoma patients. These findings, published in Cancer Cell, provide new insights into drug efficacy and may lead to better treatment monitoring strategies in cancer medicine.

“We wanted to create a monitoring tool that helps clinicians understand what is going on in the patient at a precise level, rather than looking at serial CT scans to see if the tumor grew or shrank,” said Kevin Wang, a medical student at Penn Medicine and coauthor of the study. “Clinicians could use these algorithms to personalize therapy and tailor it to each patient.”

Though every patient’s cancer is unique, one common feature is that their T cells become exhausted and peppered with checkpoint proteins.2 These proteins turn off the immune system and prevent it from killing cancer cells. Anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed death-1 (anti-PD-1) drugs work by blocking surface checkpoint proteins on T cells. Locking in these drugs at their respective checkpoints is like pulling a foot off the brakes, which helps the immune cells better destroy the cancer cells.

Anti-PD-1 and anti-CTLA-4 are common drugs in treating cancers like melanoma. However, timing is critical when deciding whether to use one or both. The research team collected blood and tissue samples from 36 melanoma patients every three weeks before and after checkpoint blockades were administered. The team built reference maps of the expression levels from single-cell RNA and T-cell receptor sequencing to confirm T cell states and track T cell dynamics from week zero to week nine of the treatment schedule. These confirmed differentiated cells and migration patterns were then analyzed on Cyclone to observe T cell responses over time, Wang said.

Patients were divided into subsets and treated with either individual blockades or combination checkpoint blockades. From these data, the researchers discovered that patients in the PD-1 blockade group, who were treated with a CTLA-4 blockade in prior cancer therapy outside of the study, had a dulled immune response compared to patients in the same group with no prior therapy. In fact, Cyclone identified more diverse T cell states in the anti-PD-1 group with no prior treatment.

The research team suspected these results based on reported checkpoint inhibitors’ characteristics and the team’s prior findings on PD-1 blockade in 2017.3 Anti-PD-1 recruits T cells to the tumor site until no more are available. With anti-CTLA-4 drugs, progenitor T cells are replenished in tissues and lymph nodes, and those cells can differentiate into T cells ready to fight. The accumulation of new progenitor T cells and replenished T cells is called clonal replacement and has been important for turning the tide on many other cancers.4

For the patients who received combination blockade administration, Cyclone measured large, diverse waves of T cell response after six and nine weeks of the combination treatment. The dual checkpoint blockades also demonstrated that CTLA-4 checkpoint blockade maintained a pool of progenitor T cells that were consistently adding to the fight against cancer.

“Anytime you can get real, mathematical synergy between drugs that is biologically explainable, that’s a wonderful finding,” said Panna Sharma, president and chief executive officer of Lantern Pharma, who was not involved in this study. “That means you can give less drugs, have more effective drugs, and everyone can become a winner.”

Website: International Research Scientist Awards

#Professor, #Lecturer, #Scientist, #Scholar, #Researcher, #Analyst, #Engineer, #Technician, #Coordinator, #Specialist, #Writer, #Assistant, #Associate, #Biologist, #Chemist, #Physicist, #Statistician, #DataScientist, #Consultant, #Coordinator, #ResearchScientist, #SeniorScientist, #JuniorScientist, #PostdoctoralResearcher, #LabTechnician, #ResearchCoordinator, #PrincipalInvestigator, #ClinicalResearchCoordinator, #GrantWriter, #R&DManager, #PolicyAnalyst, #TechnicalWriter, #MarketResearchAnalyst, #EnvironmentalScientist, #SocialScientist, #EconomicResearcher, #PublicHealthResearcher, #Anthropologist, #Ecologist#Professor, #Lecturer, #Scientist, #Scholar, #Researcher, #Analyst, #Engineer, #Technician, #Coordinator, #Specialist, #Writer, #Assistant, #Associate, #Biologist, #Chemist, #Physicist, #Statistician, #DataScientist, #Consultant, #Coordinator, #ResearchScientist, #SeniorScientist, #JuniorScientist, #PostdoctoralResearcher, #LabTechnician, #ResearchCoordinator, #PrincipalInvestigator, #ClinicalResearchCoordinator, #GrantWriter, #R&DManager, #PolicyAnalyst, #TechnicalWriter, #MarketResearchAnalyst, #EnvironmentalScientist, #SocialScientist, #EconomicResearcher, #PublicHealthResearcher, #Anthropologist, #Ecologist, #Geologist, #MaterialsScientist, #VisitingResearcher, #ScienceCommunicator, #ClinicalResearchAssociate, #RegulatoryAffairsSpecialist, #ResearchFellow, #DataAnalyst, #LaboratoryManager, #PharmaceuticalResearcher, #BiomedicalScientist, #Neuroscientist, #Geneticist, #Biostatistician, #Bioethicist, #Microbiologist, #Immunologist, #Oncologist, #Epidemiologist, #Toxicologist, #Virologist, #Zoologist, #Botanist, #MarineBiologist, #WildlifeBiologist, #AgriculturalScientist, #FoodScientist, #AtmosphericScientist, #Astronomer, #Astrophysicist, #Geophysicist, #Hydrologist, #Paleontologist, #PlanetaryScientist, #Seismologist, #PetroleumGeologist, #Oceanographer, #Hydrographer, #SoilScientist, #EnvironmentalConsultant, #ConservationScientist, #SustainabilitySpecialist, #UrbanPlanner, #Demographer, #Sociologist, #Psychologist, #CognitiveScientist, #BehavioralScientist, #Linguist, #Criminologist, #ForensicScientist, #Archaeologist, #MuseumCurator, #Archivist, #LibraryScientist, #InformationScientist, #KnowledgeManager, #PatentExaminer, #InnovationManager

More Details:


Tilte: International Research Scientist Awards

website: researchscientist.net

Visit Our Award nomination: researchscientist.net/award-nomina...

For Enquires : research@researchscientist.net


Get Connected Here;

--------------------------

--------------------------

www.facebook.com/profile.php?id=61...

www.instagram.com/researchscientist8/?next=%2F

x.com/scientistaward

in.pinterest.com/ResearchScientist...

www.blogger.com/profile/0625116998...

www.tumblr.com/blog/researchscient...