Researchers have revealed how microorganisms in the gut may influence the outcomes of patients with non-Hodgkin lymphoma undergoing chimeric antigen receptor (CAR) T-cell therapy, according to a study published by Stein-Thoeringer et al in Nature Medicine.
Background
Microorganisms live in or on almost every part of the human body and play an important role in the regulation of normal human processes. As a result, changes in the microbiome may contribute to diseases and altered responses to therapy—including cancer treatment.
It is estimated that there are 10 microorganisms for every human cell in the human body. The microbiome—which primarily comprises bacteria but also include viruses, fungi, and yeast—may interact with every human cell and influence many human processes. Recent studies have suggested that the microbiome may impact how patients with cancer respond to immunotherapies and stem cell transplants.
Study Methods and Results
In the new study, the researchers analyzed the microbiome of 172 patients with relapsed or refractory non-Hodgkin lymphoma to assess whether microorganisms have the potential to impact outcomes for those receiving CAR T-cell therapy. They discovered that patients who had taken strong, broad-spectrum antibiotics before receiving CAR T-cell therapy had less microbiome diversity, a lower response to treatment, and poorer outcomes. However, the researchers found these outcomes could also have been the result of a higher tumor burden among the patients who received antibiotics and a more suppressed immune system. Additionally, the researchers found that other factors associated with microbiome diversity—such as the patient’s country of residence, general health before treatment, and tumor burden—may have also influenced their outcomes.
After examining patient outcomes in those who received either no or lower-risk antibiotics, the researchers discovered that patients who had higher levels of the bacterium Bifidobacterium longum had an improved overall survival rate after CAR T-cell therapy compared with those whose microbiome diversity was reduced and included lower levels of the bacterium.
They used these data to create a machine learning algorithm to predict patient outcomes in those who underwent CAR T-cell therapy based on their microbiomes. Once the algorithm was tested and validated using patient data, the researchers were able to identify bacterial groups associated with either improved or poorer CAR T-cell therapy outcomes. For example, the bacterium Bacteroides eggerthii was associated with a higher likelihood of response to treatment, whereas the bacterium Bacteroides stercoris was associated with a lack of treatment response.
Conclusions
“We hope these data will lead to an improved understanding of the relationship between the microbiome and patient responses to CAR T-cell therapy. Understanding the causal nature of possible microbiome contributions to CAR T-cell therapy effectiveness and adverse effects may enable better understanding of differential CAR T-cell activation, persistence and clinical efficacy, and ultimately the prediction of response to CAR T-cell therapy prior to treatment,” concluded co–senior study author Michael Jain, MD, PhD, Assistant Member of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at the Moffitt Cancer Center.
Disclosure: The research in this study was supported by the National Cancer Institute. For full disclosures of the study authors, visit nature.com.
