Check out “What’s New in Research” to find out about discoveries and advancements from Brigham researchers. This month, we feature new research from Brigham researchers on immunotherapy for people living with HIV, face transplant rejection, evening chronotypes and emotional eating, using databases to complement randomized clinical trials and more.
Standard Immunotherapy May Be Safe for People Living with HIV and Cancer, International Patient Analysis Finds
Immune checkpoint inhibitors (ICIs) are the standard drugs for treating several types of common cancers due to their role in reinforcing the immune system’s response to cancer cells. Given that people living with HIV (PWH) may have dysfunctional immune systems, they are often excluded from ICI clinical trials due to safety and activity concerns. Researchers at the Brigham, in collaboration with several international institutions, assembled a cohort of around 400 PWH worldwide to study how their tumors respond to ICIs. They found that the ICI treatments had varying effects across different tumor types with no excess immune toxicities in PWH when compared to patients with cancer who do not have HIV. The group hopes that their study will encourage other physicians to build larger cohorts to examine the effectiveness of ICIs for PWH and potentially consider such treatments for their patients.
“Our multi-institutional analysis of a diverse cohort of about 400 patients with HIV and cancer showed that immunotherapy is safe and active in this unique patient population,” said co-first author Talal Zarif, MD, a post-doctoral research fellow at Dana-Farber Cancer Institute.
“It’s about time we advocate for broader inclusion of people living with HIV in trials of immune checkpoint inhibitors for cancer therapy,” said co-first author Amin Nassar, MD, a post-doctoral research fellow in the Brigham’s Division of General Internal Medicine.
“This study lays the groundwork for additional investigations and may serve as a valuable resource for oncologists and patients while we await results from larger clinical trials,” said co-first author Elio Adib, MD, a radiation oncology resident at the Brigham.
Read more in the Journal of Clinical Oncology.
Study Helps to Solve Mysteries of Chronic Face Transplant Rejection
Face transplantation has revolutionized the treatment of profound and debilitating facial trauma. However, a major challenge to sustainable facial transplantation remains immunologic rejection. When chronic, rejection ultimately may result in graft failure and need for re-transplantation. Such full facial grafts removed due to rejection can give researchers the unique opportunity to study the pathology of chronic rejection in depth and detail. Using sophisticated multiplex immunolabeling and digital spatial profiling approaches to mine the array of proteins and related cells responsible for the underlying pathology, a research team from Brigham and Women’s Hospital confirmed that chronic face transplant rejection results at least in part from accelerated arteriosclerosis akin to naturally occurring hardening of the arteries.
However, they also found that the underlying cause of these changes may relate to lymphocyte-mediated immune attack on the very blood vessels required to nourish the graft. And, to the researchers’ surprise, many of the culprit immune cells originated as “passenger cells” that initially resided within the donor face that ultimately react against recipient cells that migrated into the graft. Thus, rather than cells of the recipient rejecting the graft, it appeared that much of the rejection process involved cells of the graft rejecting those of the recipient.
“This resembles a phenomenon akin to graft-versus-host disease seen in some cancer patients after they receive donor bone marrow transplants to reconstitute their immune systems after myeloablative therapy,” said co-senior author George Murphy, MD, of the Department of Pathology.
“These unexpected findings now provide new and potentially practical insights into clinical management of chronic rejection of transplanted faces and limbs,” said co-senior author Christine G. Lian, MD, also of the Department of Pathology. “Our findings support the notion that arteriosclerosis in a variety of clinical settings may have an early inflammatory, immune-mediated component that ultimately results on blood vessel compromise, impaired blood flow, and tissue dysfunction.”
Read more in the American Journal of Transplantation.
Evening Chronotypes Are Associated With Emotional Eating
A person’s chronotype refers to the typical or preferred timing of their daily behaviors, including things like eating, sleeping, and physical exercise. Research has found that people who are evening types have a greater metabolic risk for obesity. However, there is a limited understanding of whether eveningness is associated with a habit like emotional eating, a primary risk factor for obesity. Investigators at the Brigham and Murcia University analyzed whether a late chronotype is associated with this behavior.
The Morningness Eveningness Questionnaire and Dim-Light Melatonin Onset were used to measure chronotypes both subjectively and objectively, while emotional eating was assessed through a survey. The researchers’ statistical analyses found that among almost 4,000 people from Spain, the United States, and Mexico, an evening chronotype was associated with emotional eating. The team concludes that planned behavioral approaches targeting emotional eating may be beneficial in limiting obesity among this chronotype group.
“The mechanisms for why evening types (also referred to as night owls) are at increased risk for having obesity and overweight are rather unclear. Our study showed that evening types scored higher on emotional eating,” said senior author, Frank Scheer, PhD, a senior neuroscientist and professor in the Brigham’s Division of Sleep and Circadian Disorders. “This provides us with a potential explanation for the reasons why there is increased body mass among evening types, and is also an exciting opportunity to test personalized behavioral therapies,” said first author, Marta Garaulet, PhD, a visiting professor in the Division of Sleep and Circadian Disorders.
Read more in Obesity.
Database Studies Can Complement Randomized Clinical Trials
Randomized controlled trials (RCT) are the gold standard for testing the safety and efficacy of interventions. But RCTs are not capable of testing all the effects of a drug in every segment of the population. Real-word studies, in which the effects of the drug or device are monitored outside of a clinical trial, have the potential to inform clinical practice, but can data collected from the real world help generate conclusions as reliably as RCTs? A new study led by investigators from Brigham and Women’s Hospital addresses this question by emulating 30 RCTs using healthcare claims data. The team found that the emulated studies generally reached similar conclusions as RCTs when design and measurements could be closely reproduced.
“Database studies can complement RCT evidence to enhance understanding of how medications work in clinical practice,” said corresponding author Shirley Wang, PhD, of the Brigham’s Division of Pharmacoepidemiology and Pharmacoeconomics. “But emulation differences, chance, and residual confounding can contribute to divergence in results and are difficult to disentangle.”
Read more in JAMA.