Breaking News
October 22, 2018 - Shorter course of trastuzumab could be an option for women with HER2+ early breast cancer
October 22, 2018 - Map of Mouse Hippocampus Could Be Weapon Against Alzheimer’s
October 22, 2018 - Psychotropic polypharmacy is common in Alzheimer’s disease
October 22, 2018 - Texas A&M and UTA establish Texas Genomics Core Alliance
October 22, 2018 - Analyzing mouse’s potential as animal model of decision-making
October 22, 2018 - Radiotherapy can prolong survival in prostate cancer
October 22, 2018 - A genetic mutation involved in relapse
October 21, 2018 - Report reveals growing impact of cannabis on young people
October 21, 2018 - NSF awards $5 million grant to help scientists magnify societal impact of research
October 21, 2018 - Fertility Rates Down for Each Urbanization Level 2007 to 2017
October 21, 2018 - Genetically engineered 3-D human muscle transplant in a murine model
October 21, 2018 - Moms’ tight work schedules may affect their children’s sleep
October 21, 2018 - AHA: No Direct Link Between Preeclampsia and Cognitive Impairment, Study Finds
October 21, 2018 - Weight loss success linked with active self-control regions of the brain
October 21, 2018 - Scripps researchers successfully test potential new smoking-cessation treatment in rodents
October 21, 2018 - More accurate and less stressful way to measure a baby’s heartbeat
October 21, 2018 - Researchers show better cardiorespiratory fitness leads to longer life
October 21, 2018 - Healthy candies for diabetic patients
October 21, 2018 - Environment impact of microplastics remains unclear
October 21, 2018 - Antibiotics for appendicitis? Surgery often not needed
October 21, 2018 - AHA and AMA recognize more than 800 medical practices, health systems for blood pressure control
October 21, 2018 - Scientists obtain clearest ever image of Ebola virus protein
October 21, 2018 - Study reveals connection between two proteins known to be hyperactive in cancer
October 21, 2018 - Gabapentin Beats Pregabalin for Chronic Sciatica
October 21, 2018 - Cosmetic surgeons offering incomplete information for breast augmentation customers
October 21, 2018 - Chronic sleep disruption in early adult life accelerates AD-related tau pathology
October 21, 2018 - Take 10 for Mindfulness – Drugs.com MedNews
October 21, 2018 - Length of breathing disruption in OSA may be better predictor of mortality risk
October 21, 2018 - ApoE4 gene linked with chronic inflammation increases risk for Alzheimer’s disease
October 21, 2018 - Mother-daughter conflict associated with suicide risk in abused adolescent girls
October 21, 2018 - Scientists molding bacteria into unnatural shapes
October 21, 2018 - High diet quality associated with lower risk of death in colorectal cancer patients
October 21, 2018 - Discharged mental health patients ‘at greater risk of dying’
October 21, 2018 - Research provides insight into neurobiology of aggression and bullying
October 21, 2018 - As billions in tax dollars flow to private Medicaid plans, Who’s minding the store?
October 21, 2018 - Neuroscientists identify brain region that appears to be related to food preference decisions
October 21, 2018 - Deaths related to air pollution in the U.S. decreased by 47% between 1990 and 2010
October 21, 2018 - Study shows correlation between spatial memory and the sense of smell
October 21, 2018 - Increased cardiorespiratory fitness associated with reduced long-term mortality
October 21, 2018 - IU researchers receive $1.55 million from NIH to improve chronic-disease management
October 21, 2018 - Income and wealth affect the mental health of Australians, study shows
October 21, 2018 - Patients with hypertension and psoriasis more often require cardiovascular interventions
October 20, 2018 - Leading hip-hop videos depict use of tobacco and marijuana products, study finds
October 20, 2018 - Dose Range of IV Ketamine for Adjunct Tx of Depression Tested
October 20, 2018 - Infants can distinguish between leaders and bullies, study finds
October 20, 2018 - Mad Cow disease found on Aberdeenshire farm
October 20, 2018 - Study identifies factors associated with prescription opioid misuse among students
October 20, 2018 - Scientists uncover key regulator of mTORC1 in cancer growth
October 20, 2018 - Pounds Regained After Weight-Loss Op Can Tell Your Doc a Lot
October 20, 2018 - Sending parents letters to fight childhood obesity doesn’t work
October 20, 2018 - Supervised aerobic exercise can support major depression treatment
October 20, 2018 - Mindfulness-based program effective for reducing stress in infertile women
October 20, 2018 - Molecule capable of halting and reverting neurodegeneration caused by Parkinson’s disease identified
October 20, 2018 - Midazolam-mediated alterations of PER2 expression may have functional consequences during myocardial ischemia
October 20, 2018 - Sweat bees are ideal for studying the genes underlying social behavior
October 20, 2018 - Weight loss success associated with brain areas involved in self-control
October 20, 2018 - KHN’s ‘What the Health?’ Republicans’ preexisting political problem
October 20, 2018 - Research provides a more complete picture of suffering caused by terrorist attacks
October 20, 2018 - Eradicating Helicobacter pylori infections may be a key treatment for Parkinson’s disease
October 20, 2018 - Breast Cancer as a Dynamic Disease
October 20, 2018 - University of Pittsburgh wins NSF grant for big data research to prevent complications from anesthesia
October 20, 2018 - Skin-to-skin contact may promote attachment between parents and preterm infants
October 20, 2018 - Recommendations Developed to Verify NGT Placement in Children
October 20, 2018 - Weight loss can be boosted fivefold thanks to novel mental imagery technique
October 20, 2018 - Children with autism are more likely to be overweight, obese
October 20, 2018 - Nurses making conscientious objections to ethically-relevant policies lack support
October 20, 2018 - Prion strain diversity may be greater than previously thought
October 20, 2018 - Antidepressant treatment may lead to improvements in sleep quality of patients with depression
October 20, 2018 - Study reports increased risk of death in children with inflammatory bowel disease
October 20, 2018 - Number of Autism Genes Now Tops 100
October 20, 2018 - Total diet replacement programmes are effective for treating obesity
October 20, 2018 - CLARIOstar used for fluorescence measurements on CSIRO’s purpose-built research vessel
October 20, 2018 - People with more copies of AMY1 gene digest starchy carbohydrates faster
October 20, 2018 - Case Comprehensive Cancer Center wins NIH grant to study health disparities
October 20, 2018 - Newly discovered compound shows potential for treating Parkinson’s disease
October 20, 2018 - High rate of non-adherence to hormonal therapy found among premenopausal early breast cancer patients
October 20, 2018 - Immunotherapy medicine found to be effective in treating uveitis
October 20, 2018 - The Pistoia Alliance Calls for Greater Collaboration to Realise Benefits of Innovation and Announces Winners of the 2018 President’s Startup Challenge
October 20, 2018 - Female internists consistently earn less than men
October 20, 2018 - Stanford team looks at dangers of teens’ vaping habits
Researchers discover potential regulator essential for killer T cells to reside in tumors

Researchers discover potential regulator essential for killer T cells to reside in tumors

image_pdfDownload PDFimage_print

Researchers report the discovery that a protein called “Runx3” programs killer T cells to establish residence in tumors and infection sites.

During infection or tumor growth, a type of specialized white blood cells called CD8+ T cells rapidly multiply within the spleen and lymph nodes and acquire the ability to kill diseased cells. Some of these killer T cells then migrate where required to vanquish the germs or cancers.

But how do killer T cells “learn” to leave their home base and amass within specific tissues like the skin, gut, and lung, or solid tumors? Finding the factors that cause T cells to function beyond the lymphoid system and in sites of infection or cancer has proven a tough challenge, but it’s essential for developing cancer-fighting immunotherapy strategies.

Writing in the journal Nature, researchers from The Scripps Research Institute and the University of California, San Diego report the discovery that a protein called “Runx3” programs killer T cells to establish residence in tumors and infection sites.

“Runx3 works on chromosomes inside killer T cells to program genes in way that enables the T cells to accumulate in a solid tumor,” said Matthew Pipkin, Ph.D., associate professor in the Department of Immunology and Microbiology on the Florida campus of The Scripps Research Institute.

The paper, “Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumors,” appears in Nature’s Dec. 14 issue.

There are two main strategies in cancer immunotherapy that employ killer T cells, Pipkin said. Checkpoint inhibitor blockade unleashes killer T cells, prompting them to accumulate in tumors more aggressively. Adoptive cell transfer, meanwhile, involves re-infusing a patient’s own immune cells after they have been engineered in the lab to recognize and destroy the patient’s specific cancer.

The adoptive cell transfer strategy has worked stunningly well in some blood cancers associated with the lymphoid system, so far. But there appears to be less efficient activity of T cells in solid tumors, Pipkin said.

“The gene programs and signals for how the T cells take up residence in tissues outside of the general circulation was not really well understood,” Pipkin said.

To discover factors that control T cell residency beyond the lymphoid system, Pipkin’s team worked collaboratively with the laboratory of UC San Diego’s Ananda Goldrath, who compared the gene expression of CD8+ T cells found in non-lymphoid tissue to those found in the general circulation. From a list of potential factors, they employed an RNA interference screening strategy which can test the actual function of thousands of factors simultaneously. Pipkin’s lab had developed the screening strategy in collaboration with Shane Crotty at the La Jolla Institute for Allergy and Immunology.

“We found a distinct pattern,” Pipkin said. “The screens showed that Runx3 is one at the top of a list of regulators essential for T cells to reside in nonlymphoid tissues.” Moreover, Runx3 was able to engage a specific gene program that is found in natural tissue-resident and tumor infiltrating CD8+ T cells, he said.

The group further assessed whether Runx3 had a role in directing white blood cells that attack solid tumors in mouse melanoma models. They found that adoptive cell transfer of cancer-specific killer T cells that overexpressed Runx3 delayed tumor growth and prolonged survival, while mouse models treated with those lacking Runx3 fared much worse than normal.

“If we enhance Runx3 activity in the cells, the tumors are significantly smaller and there is greater survival compared to the control group,” Pipkin said.

Knowing that modulating Runx3 activity in T cells influences their ability to reside in solid tumors opens new opportunities for improving cancer immunotherapy, Pipkin said.

“The upshot is we could probably use Runx3 to reprogram adoptively transferred cells to help drive them to amass in solid tumors,” he said. He added that a collaboration of specialists energized the research. “It was a fantastic collaboration, it all came together very quickly,” Pipkin said.

Source:

http://www.scripps.edu/news/press/2017/20171111pipkin.html

Tagged with:

About author

Related Articles