Significant strides have been made in leveraging checkpoint inhibitor therapy to combat a number of cancers over the recent years. However, not all malignancies respond to these therapies, and those that do often become resistant, or are discontinued due to adverse reactions within the immune system. Now, researchers have shown that gut microbiota are one of the key factors influencing the success of immunotherapy targeting PD-L1 and PD-1 gene expression.
The study was published in the journal Cancer Biology and Medicine. The research team undertook a comprehensive review focused on seeking to understand how microbial ecosystems within the gut impact how patients respond to checkpoint inhibitors targeting PD-L1 and PD-1.
They analyzed clinical trials, preclinical studies and available multi-omics data to ascertain how bacterial populations influence toxicity, immune system activation, and sensitivity to immunotherapy. Their findings show that interventions targeting tweaking the microbiota could boost immunotherapy and advance personalized cancer care. The interventions include transplanting fecal microbiota, engineering bacteria and the use of probiotics.
The researchers say microbiota in the gut are an immune organ powering metabolic pathways in ways that could reshape the systems combating tumors because they interconnect multiple biological pathways. Some of the ways through which this influence is exerted, according to the study authors, are delaying the exhaustion of the immune system, improving antigen presentation, and regulating how T-cells are differentiated.
The authors say the data they reviewed revealed many ways through which gut microbiota interventions promoted immunotherapy against cancer. For example, transplanting fecal microbiota helped to reduce adverse events related to the administration of immunotherapy in patients having advanced cancers. Patients who had become unresponsive to the therapies also exhibited revived responsiveness after microbiota interventions.
The researchers also found data showing that testing for certain microbial markers helped to predict which patients could respond to particular checkpoint inhibitor therapies.
The team emphasizes that their findings show that it is erroneous to focus on tumor genetics alone as a predictor of treatment success. This is because patient responses to treatment are influenced by many factors, with gut microbiota playing a key role. Many systems are interconnected, so cancer therapy needs to factor in several elements if efficacy rates are to improve, the researchers argue.
They call for including microbiota tracking before, during and after therapy is administered so that needed interventions like modulating the diet, transplanting fecal microbiota or use of probiotics can be integrated in the treatment plan where such an intervention is warranted to bolster and sustain treatment outcomes.
The insights obtained from this research could have additional applications in treating inflammatory and autoimmune diseases. For oncology, these findings are eye-opening and firms like Calidi Biotherapeutics Inc. (NYSE American: CLDI) could have several illuminating moments that may enrich their own work in advancing oncolytic virus therapy indicated for different cancers.
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