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    Laura McLane and Mike Betts -Purified human CD8 T-cells were stained with a-T-bet (green), a-Lamin A (pink), and DAPI (blue) and imaged on a multilaser-based spinning disk confocal microscope (Zeiss). T-bet can be localized to both the nuclear and cytoplasmic compartments of specific subsets of human CD8 T-cells.

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    3D image of the inflamed meningeal membrane of a CX3CR1-GFP reporter mouse infected with Toxoplasma gondii. The dura mater that surrounds the brain is blue, blood vessels are labeled red and microglia and macrophages are green. Contributors for image are ChristophKonradt and Chris Hunter.

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    Time series of cells expressing GFP-tagged ebola viral protein VP40, pseudocolored as a fluorescence intensity heatmap. The contributors for image are: Gordon Ruthel, Xiaohong Liu, Ron Harty, and Bruce Freedman.

Archived News

IFI Faculty Members appointed to editorial board of new journal

Institute for Immunology faculty members Robert Vonderheide, MD and Carl June, MD have been appointed to the editorial board of a new journal, Cancer Immunology Research (CIR). Dr. Vonderheide has been appointed Deputy Editor and Dr. June has been named Senior Editor of the new publication. Cancer Immunology Research plans to publish outstanding original articles reporting major advances in cancer immunology that span the discipline from basic investigations in host–tumor interactions to developmental therapeutics in model systems, early translational studies in patients, and late–stage clinical trials. The journal’s special features will include “Masters of Immunology”—primers by leading immunologists—and “Cancer Immunology at the Crossroads”—perspectives that highlight the intersection of immunology with other areas of cancer research and allied disciplines.

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Leukemia Patients Remain in Remission More Than Two Years After Receiving Genetically Engineered T Cell Therapy

December 9, 2012

Nine of twelve leukemia patients who received infusions of their own T cells after the cells had been genetically engineered to attack the patients’ tumors responded to the therapy, which was pioneered by scientists in the Perelman School of Medicine at the University of Pennsylvania. Penn Medicine researchers will present the latest results of the trial today at the American Society of Hematology’s Annual Meeting and Exposition. The clinical trial participants, all of whom had advanced cancers, included 10 adult patients with chronic lymphocytic leukemia treated at the Hospital of the University of Pennsylvania (HUP) and two children with acute lymphoblastic leukemia treated at the Children’s Hopsital of Philadelphia. Two of the first three patients treated with the protocol at HUP remain healthy and in full remissions more than two years after their treatment, with the engineered cells still circulating in their bodies. The findings reveal the first successful and sustained demonstration of the use of gene transfer therapy to turn the body’s own immune cells into weapons aimed at cancerous tumors.

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Penn Team Identifies Molecular Root of “Exhausted” T Cells in Chronic Viral Infection

November 29, 2012

When you get an acute infection, such as influenza, the body generally responds with a coordinated response of immune-cell proliferation and attack that rapidly clears the pathogen. Then, their mission done, the immune system stands down, leaving a population of sentinel memory cells to rapidly redeploy the immune system in the event of reinfection. But what about chronic infection? In the case of such pathogens as hepatitis C, HIV, and malaria, the body and the pathogen essentially fight to a prolonged stalemate, neither able to gain an advantage. Over time, however, the cells become “exhausted” and the immune system can collapse, giving the pathogen the edge. Now, a new study by researchers at the Perelman School of Medicine, University of Pennsylvania is showing just how that happens. The findings also suggest a novel therapeutical approach that might be used to shift the balance of power in chronic infections. The study appears in the November 30 issues of Science. The team, led by E. John Wherry, PhD, associate professor of Microbiology and Director of the Institute for Immunology, used a mouse model of chronic viral infection to map the T-cell response that arises when the immune system is on an extended war footing.

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Institute of Medicine Elects Six New Members From Penn

October 15, 2012

Six professors from the University of Pennsylvania, representing four schools, have been elected members of the Institute of Medicine (IOM), one of the nation’s highest honors in biomedicine. Established in 1970 by the National Academy of Sciences, IOM has become recognized as a national resource for independent, scientifically informed analysis and recommendations on health issues. The new Penn IOM members include Carl June, the Richard W. Vague Professor in Immunotherapy, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, and the Program Director of Translational Research, Abramson Family Cancer Research Institute.

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Lowering the Age of Scientific Independence

October 4, 2012

Just over five years ago, Greg Sonnenberg, PhD, research associate in the Division of Gastroenterology and the Institute for Immunology, was tossing his mortarboard in the air at his now undergraduate alma mater SUNY Buffalo. This month, he will be starting his first independent research position, all before turning 30, effectively bypassing the ubiquitous postdoctoral phase of a typical career in biomedical research. Sonnenberg is one of 14 early–career scientists supported this year with an EIA, part of the second annual cohort of awardees.

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Penn Immunologists Find a Molecule That Puts the Brakes on Inflammation

Septemer 28, 2012

A new study led by University of Pennsylvania researchers has now identified a crucial signaling molecule involved in counterbalancing the immune system attack. “The immune response is like driving a car,” said Christopher Hunter, professor and chair in the Department of Pathobiology in Penn’s School of Veterinary Medicine. “You hit the accelerator and develop this response that’s required to protect you from a pathogen, but, unless you have a brake to guide the response, then you’ll just careen off the road and die because you can’t control the speed of the response.” The research to characterize this immune system “brake” was led by Hunter and Aisling O’Hara Hall, a doctoral candidate in the Immunology Graduate Group.

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Good Bugs Gone Bad: Microbes that Promote Normal Health Can “Turn Bad” if Found Outside the Intestine

June 6, 2012

The healthy human intestine is colonized with over 100 trillion beneficial, or commensal, bacteria of many different species. In healthy people, these bacteria are limited to the intestinal tissues and have a number of helpful properties, including aiding in the digestion of food and promoting a healthy immune system. However, when it comes to commensal bacteria, location is key. While commensal bacteria in the intestine provide positive effects, several chronic human diseases, including HIV/AIDS, inflammatory bowel disease, viral hepatitis, and obesity are associated with the spread of these intestinal commensal bacteria to the blood stream and other peripheral tissues, which can cause chronic inflammation. ‘Good bugs’ that promote normal health can ‘turn bad’ if found in the wrong location. Now, David Artis, Ph.D., associate professor of Microbiology and Gregory F. Sonnenberg, Ph.D., a postdoctoral researcher in the Artis lab, have identified that immune cells, called innate lymphoid cells, are resident in the intestinal tissues of healthy humans, mice, and non-human primates, and are critical in limiting the location of commensal bacteria.

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T Cells ‘Hunt’ Parasites Like Animal Predators Seek Prey, a Penn Vet-Penn Physics Study Reveals

May 29, 2012

By pairing an intimate knowledge of immune–system function with a deep understanding of statistical physics, a cross–disciplinary team at the University of Pennsylvania has arrived at a surprising finding: T cells use a movement strategy to track down parasites that is similar to strategies that predators such as monkeys, sharks and blue–fin tuna use to hunt their prey. With this new insight into immune–cell movement patterns, scientists will be able to create more accurate models of immune–system function, which may, in turn, inform novel approaches to combat diseases from cancer to HIV/AIDS to arthritis.

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Inner Weapons Against Allergies: Gut Bacteria Control Allergic Diseases, Perelman School of Medicine Study Finds

March 26, 2012

David Artis, Ph.D., Associate professor of Microbiology, along with postdoctoral fellow David Hill, Ph.D., from the Perelman School of Medicine, and collaborators from The Children’s Hospital of Philadelphia and institutions in Japan and Germany, have found that these commensal bacteria might play an important role in influencing and controlling allergic inflammation. The commensal relationship that develops between humans and internal bacteria is one in which both humans and bacteria derive benefits. The study, appearing this week in Nature Medicine, suggests that therapeutic targeting of immune cell responses to resident gut bacteria may be beneficial in treating allergic diseases.

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New Hope of a Cure for H.I.V.

November 28, 2011

Medical researchers are again in pursuit of a goal they had all but abandoned: curing AIDS. Until recently, the possibility seemed little more than wishful thinking. But the experiences of two patients now suggest to many scientists that it may be achievable. One man, the so–called Berlin patient, apparently has cleared his H.I.V. infection, albeit by arduous bone marrow transplants.

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An Immune System Trained to Kill Cancer

September 12, 2011

A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose. Special cell–culturing techniques may have contributed to the lab’s success. Doctors removed a billion of his T–cells — a type of white blood cell that fights viruses and tumors — and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig’s veins. At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst. A few weeks later, the fevers were gone. And so was the leukemia.

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New leukemia treatment exceeds ‘wildest expectations’

September 12, 2011

Doctors have treated only three leukemia patients, but the sensational results from a single shot could be one of the most significant advances in cancer research in decades. And it almost never happened.In the research published Wednesday,doctors at the University of Pennsylvania say the treatment made the most common type of leukemia completely disappear in two of the patients and reduced it by 70 percent in the third. In each of the patients as much as five pounds of cancerous tissue completely melted away in a few weeks, and a year later it is still gone. The results of the preliminary test “exceeded our wildest expectations,” says immunologist Dr. Carl June a member of the Abramson Cancer Center&rsqou;s research team.

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Penn Study Shows Link Between Immune System Suppression and Blood Vessel Formation in Tumors

July 13, 2011

Targeted therapies that are designed to suppress the formation of new blood vessels in tumors, such as Avastin (bevacizumab), have slowed cancer growth in some patients. However, they have not produced the dramatic responses researchers initially thought they might. Now, research from the Perelman School of Medicine at the University of Pennsylvania might help to explain the modest responses. The discovery, published in the July 14 issue of Nature, suggests novel treatment combinations that could boost the power of therapies based on slowing blood vessel growth (angiogenesis). The Penn investigators, led by George Coukos, MD, PhD, Celso–Ramon Garcia Professor of Reproductive Biology, found that ovarian cancer cells grown under low oxygen conditions—which promote blood vessel formation—secrete chemical signals that suppress the patient’s immune system, preventing it from killing off the abnormal cancer cells.

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Penn Gets $225 Million for Its School of Medicine

May 10, 2011

The University of Pennsylvania has received a $225 million gift, the largest in its history, from Raymond G. Perelman and his wife, Ruth, for its medical school, which will be renamed the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania. Amy Gutmann, the president of the university, said the Perelmans’ gift was transformational. “It’s the triple crown for our school of medicine,” she said. “It’s going to enable us to have the best students, with enormously increased financial aid, and to recruit the most eminent faculty and provide extraordinary research.”

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Penn study leads to new idea in treating pancreatic cancer

March 25, 2011

Sometimes in science, what you get wrong can be just as important as what you get right. Researchers at the University of Pennsylvania Perelman School of Medicine set out two years ago to prove that a new drug could marshal T cells, key players in the immune system, against pancreatic cancer. That didn&rsqou;t happen. Instead, the experimental antibody turned more primitive immune-system cells that often get co–opted into helping pancreatic cancer tumors against part of the tumor structure. Tumors shrank substantially in some patients, and median survival time lengthened by two months, to 7.4 months. That doesn&rsqou;t sound like much, but, with a notoriously deadly cancer, it was a step forward.

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Promising new gene therapy for HIV immunity

March 3, 2011

In a feat that is renewing hopes for conquering AIDS, researchers have genetically engineered patients’ vital immune cells to make them resistant to HIV infection. To confer this invulnerability, scientists took the immune cells from HIV–positive patients’ own blood, then snipped out a single gene—the first time such a precise alteration has been achieved on a meaningful scale. When put back in the patient, the cells no longer make a receptor that HIV needs to enter the cell, effectively blocking the virus.

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New $25.5 million Abramson family gift to fund cancer research at Penn Medicine

February 17, 2011

For years, Madlyn and Leonard Abramson have given millions of dollars to fund cancer research at Penn Medicine, including the naming of the Abramsom Cancer Center and the establishment of the Abramson Family Cancer Research Institute. Penn Medicine’s largest donors have given $25.5 million more to support basic science and translational research progress in the Abramson Family Cancer Research Institute, which is among the nation’s preeminent incubators for drug discovery and development of new ways to diagnose and treat patients.

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Border Patrol: Immune Cells Protect Body from Invaders, According to Penn Researchers

Feburary 4, 2011

So-called barrier sites—the skin, gut, lungs—limit the inner body’s exposure to allergens, pollutants, viruses, bacteria, and parasites. Understanding how the immune system works in these external surfaces has implications for understanding such inflammatory diseases as asthma, psoriasis, IBD, and food allergies, all of which occur at the body’s barriers. David Artis, Ph.D., professor of Microbiology and Gregory F. Sonnenberg, a predoctoral fellow in the Artis lab, have identified an immune cell population that acts as the body’s border patrol with the outside world. They discovered that these lymphoid tissue inducer cells maintain immunity in the intestine of mice. The research appeared in the most recent online issue of Immunity.

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Penn Scientists Identify New Role for Protein Molecule That Inhibits Response of Immune-System Cells

November 7, 2010

An international group of scientists, with lead researchers in Penn’s School of Veterinary Medicine and School of Medicine, has shown the unique ability of a protein subunit called IL-27p28 to bind with a key cell receptor (gp130), effectively preventing it from transmitting signals necessary for triggering an immune response. Regulating the production of the molecule could lead to new, targeted interventions for cancer, asthma, lupus, multiple sclerosis, arthritis and other diseases. “Lots of pharmaceutical companies are focused on possible targets upstream or downstream of this key receptor,” said Christopher Hunter, professor and chair of pathobiology in Penn Vet. “Here, we’ve discovered a natural molecule that limits signaling through that receptor. There’s already genetic data out there saying this protein is important in human medicine. We agree with that, but maybe it works a different way than we thought before. Then, having this information means that this natural molecule provides a new way to manage different types of inflammatory diseases.”

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Penn Study Shows Two–Sided Immune Cell Could be Harnessed to Shrink Tumors

October 27, 2010

A recently identified immune cell that directs other cells to fight infection plays a critical role in regulating the immune system in both health and disease. Researchers from the University of Pennsylvania School of Medicine have discovered how a stimulatory molecule and a protein found on the membrane of another immune cell make T helper 17 cells multi–taskers of sorts. Th17 cells protect the body against infection and cancer, but are also culprits in some autoimmune diseases and out–of–control, cancerous cell growth. This new understanding that Th17 cells manage to play both sides of the fence suggests that targeting or inhibiting the involved protein pathways might be a new way to treat cancer, chronic infection, and some autoimmune diseases. Previous studies have linked excessive amounts of Th17 cells in the body to such autoimmune diseases as multiple sclerosis, psoriasis, rheumatoid arthritis, and Crohn’s disease.

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