Cancer
Short Bouts Of Exercise May Boost Efficacy Of Some Types Of Cancer Treatment
A burst of vigorous-intensity exercise could aid the efficacy of rituximab, an antibody therapy that is commonly used to treat chronic lymphocytic leukemia (CLL), new research shows.
Scientists at the Universities of Birmingham and Bath, in the United Kingdom, have published a study in the journal Brain, Behavior, and Immunity, which looked at a participant group of 20 people with CLL.
These had not received any cancer treatment before, and took part in a round of cycling for 20 to 30 minutes as part of the study.
The researchers found that this type of exercise — in which participants were instructed through moderate- to vigorous-intensity cycling — raised the number of anti-cancer immune cells, or natural killer cells, by 254%.
In combination with rituximab, which attaches to a protein on cancer cells that helps the natural killer cells identify and kill them, the anti-cancer cells were twice as effective in blood samples taken immediately after exercise.
"This study is the first to show that a single bout of vigorous intensity cycling exercise improves rituximab-mediated ADCC [antibody-dependent cellular cytotoxicity] against autologous CLL cells ex vivo," the authors write.
"The mobilisation of CD5+CD19+ CLL cells and their subsets in response to cycling exercise in this study is a novel finding not previously described. CLL cells possess a similar phenotype to that of healthy B-cells (e.G., CD19) and these cells may increase up to 100% following a bout of vigorous cycling in healthy humans," they conclude.
Catherine S. Diefenbach, MD, the director of the Clinical Lymphoma Program at the Perlmutter Cancer Center at NYU Langone Health, who was not involved in the research, told Medical News Today that while the study's results were interesting, there are still unanswered questions, most prominently due to the very small sample size.
"This is a small pilot study of 20 patients in a controlled situation — restricted to exercise in a set fashion — with some intriguing biologic findings of exercise activation NK cell activity and Rituxan [brand name for rituximab] induced CLL killing," she explained.
"However, this data needs to be validated in larger studies with a more heterogenous patient population," cautioned Diefenbach. "It is also not clear how this finding impacted clinical outcome or whether it did have any bearing on response to therapy, or disease stability."
"This study does not demonstrate that exercise impacted the clinical trajectory of CLL, merely that it induced enhanced Rituxan directed CLL cytotoxicity," she pointed out. "There are no randomized clinical trials in the cancer space that I know of that use exercise as an intervention and have demonstrated an improvement in clinical outcome."
Wael Harb, MD, a board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, CA, who likewise was not involved in the research, also told MNT that it would be hard to extrapolate a broad template of treatment from of this study.
"The patient who will be able to do vigorous exercise maybe has a different immune system compared to people who don't. How can we generalize this data or this information to others because of the feasibility of the exercise, and because of the sample size?" Dr. Harb wondered, adding that because the study was based on blood samples — ex vivo — it is hard to determine what is going on inside of the body.
"Most important is how this will impact outcome, right? So you need to have a long-term outcome to see — does this really make a difference in response to treatment, [in terms of] leukemia pain remission? We would require more structural study to do that and expose randomized patients to different regimens with the same treatment — with rituximab — or rituximab-based treatments and we can add different exercise programs to that."
– Wael Harb, MD
While many cancer treatments, especially those that involve chemotherapy or surgery, can cause extreme fatigue that can prevent physical activity, there is growing evidence that exercise can stimulate immune cells.
Harb explained that physical activity has been well-documented as a way to boost the body's immune system to fight cancer cells. He cited several studies from the past few years that examined the effects of short bursts of exercise and more regular patterns of activity.
"We recommend being active and exercising — we do believe that there's a body of evidence that exercise during cancer treatment can help the immune system and now more than ever before we understand the role of the immune system in fighting cancer," he said, speaking of clinicians' advice.
"[I]n fact, we a lot of the newer therapies for cancer are immune-based therapies that help activate the immune system to fight cancer," Harb added, though he had some further words of caution regarding exercise as an add-on to cancer therapy.
"The vigorous exercise portion — that's a little bit challenging. It depends on, basically, to the person's ability to exercise, age, comorbidities that make it more difficult. So there may be some practical issues there when we talk about vigorous exercise; it makes it limited to what patient might be able to participate."
– Wael Harb, MD
Cancer Breakthrough: Scientists Discover Game-Changing New Type Of T Cells
Researchers at the University of Houston, led by Navin Varadarajan, have discovered a new subset of T cells, termed CD8-fit, which are associated with improved outcomes in T-cell therapies for cancer. Using a combination of the TIMING method and single-cell RNA sequencing, the team identified a molecular signature in these T cells that correlates with long-term positive clinical outcomes. The findings, which also involve collaborations with prestigious institutions and contributions from notable graduate and post-doctoral researchers, could revolutionize personalized T-cell therapies for various cancers.
Researchers from the University of Houston identified CD8-fit T cells with high motility and serial killing abilities, potentially enhancing T-cell cancer therapies. The study used the TIMING approach and RNA sequencing, revealing molecular signatures that predict positive patient outcomes.
A group of cancer researchers from the University of Houston has identified a new type of T cells, which could enhance the results for patients undergoing T-cell therapies.
T cell-based immunotherapy holds immense potential in combating and often eradicating cancer. This approach activates and engineers a patient's immune system, specifically their T cells, to identify, attack, and destroy cancer cells. As a result, the body's own T cells function as living drugs.
While T-cell immunotherapy has revolutionized cancer treatment, there is still much to learn. Unfortunately, not all patients respond to these therapies, so a better understanding of the properties of engineered T cells is necessary to improve clinical responses.
One such study, supported by a grant from the National Institutes of Health, was reported in Nature Cancer on May 15 by the laboratory of Navin Varadarajan, M.D. Anderson Professor in the William A. Brookshire Department of Chemical and Biomolecular Engineering. The study uses the patented TIMING (Timelapse Imaging Microscopy in Nanowell Grids) approach which applies visual AI to evaluate cell behavior, movement, and ability to kill.
Navin Varadarajan, University of Houston M.D. Anderson Professor of chemical and biomolecular engineering, has published in Nature Cancer the discovery of new cancer-killing T cells. Credit: University of Houston
Discovery of CD8-Fit T Cells"Our results showed that a subset of T cells, labeled as CD8-fit T cells, are capable of high motility and serial killing, found uniquely in patients with clinical response," reports first author and recent UH graduate Ali Rezvan in Nature Cancer. In addition to the UH team, collaborators include Sattva Neelapu and Harjeet Singh, The University of Texas MD Anderson Cancer Center, Houston; Mike Mattie, Kite Pharma; Nabil Ahmed, Texas Children's Hospital, Baylor College of Medicine, Houston; and Mohsen Fathi, CellChorus.
To discover the CD8-fit cells, the team used TIMING to track interactions between individual T cells and tumor cells across thousands of cells and integrated the results with single-cell RNA sequencing data.
"Chimeric antigen receptors (CAR) T cells used for the treatment of B cell malignancies can identify T-cell subsets with superior clinical activity. Using infusion products of patients with large B cell lymphoma, we integrated functional profiling using TIMING with subcellular profiling and scRNA-seq to identify a signature of multifunctional CD8 T cells (CD8-fit)," said Rezvan. "We profiled these cells using single-cell RNA sequencing to identify the CD8-fit molecular signature that could be used to predict durable patient outcomes to T-cell therapies and validated our findings with independent datasets."
The team also found that the CD8-fit signature is present in pre-manufactured T cells, longitudinally persists in patients post-infusion, and most importantly, is associated with long-term positive clinical responses. According to the researchers, it is likely that these T cells can drive clinical benefit in other tumors.
"This work illustrates the excellence of graduate students Ali Rezvan and Melisa Montalvo; and post-doctoral researchers Melisa Martinez-Paniagua and Irfan Bandey among others," said Varadarajan.
CellChorus, a spinoff from Varadarajan's Single Cell Lab at UH, is developing the AI-powered TIMING platform. The company recently announced a $2.5 million Small Business Innovation Research grant from the National Center for Advancing Translational Sciences of the National Institutes of Health to advance TIMING for cell therapy applications.
Reference: "Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling" by Ali Rezvan, Gabrielle Romain, Mohsen Fathi, Darren Heeke, Melisa Martinez-Paniagua, Xingyue An, Irfan N. Bandey, Melisa J. Montalvo, Jay R. T. Adolacion, Arash Saeedi, Fatemeh Sadeghi, Kristen Fousek, Nahum Puebla-Osorio, Laurence J. N. Cooper, Chantale Bernatchez, Harjeet Singh, Nabil Ahmed, Mike Mattie, Adrian Bot, Sattva Neelapu and Navin Varadarajan, 15 May 2024, Nature Cancer.DOI: 10.1038/s43018-024-00768-3
New Study Of Cancer Cells Hopes To Improve Diagnosis & Treatment
Researchers at the Hebrew University of Jerusalem say they have developed a way to accurately predict the behavior of cancer cells, which will advance diagnosis and treatment of the disease.
The new diagnostic tool uses AI machine learning combined with nanoinformatics (observing nanomaterials) to classify cancer cell behavior in individual patient biopsies, potentially paving the way for personalized monitoring of the progression of the disease and the impact of treatments.
The study was led by Hebrew University doctoral student Yoel Goldstein and Prof. Ofra Benny from its School of Pharmacy in the Faculty of Medicine, working with Prof. Tommy Kaplan, the head of the Department of Computational Biology at the School of Engineering and Computer Science.
"Our method is novel in its ability to distinguish between cancer cells that appear identical, but behave differently at a biological level," said Goldstein.
"This precision is achieved through algorithmic analysis of how micro and nanoparticles are absorbed by cells. The ability to collect and analyze new types of data brings up new possibilities for the field, with the potential to revolutionize clinical treatment and diagnosis through the development of new tools," he said.
"The research has paved the way for new types of clinical tests that could significantly impact patient care," said Benny.
"This discovery allows us to potentially use cells from patient biopsies to quickly predict disease progression or chemotherapy resistance and could also lead to innovative blood tests that assess the efficacy of targeted immunotherapy treatments."
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