Scientists identify gut bacteria that increase immunotherapy efficacy
Immunotherapy has significantly improved cancer treatment. But less than half of patients with melanoma respond well to immunotherapy. If we can find ways to increase their response rate, it will lead to considerable improvement in the treatment of melanoma.
Now, scientists are one step toward this goal. Published in Science today, a study titled "The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients" has demonstrated that some bacteria in the human body are able to improve the efficacy of anti–PD-1 immunotherapy in patients with metastatic melanoma.
The work is carried out by eight researchers from the University of Chicago. Professor Thomas Gajewski of the university is the corresponding author. Other researchers include Vyara Matson, Jessica Fessler, Riyue Bao, Tara Chongsuwat, Yuanyuan Zha, Maria-Luisa Alegre, and Jason Luke. Professor Gajewski's lab is committed to understanding the regulation of T cell activation and differentiation, in a hope to use this information to find ways to promote anti-tumor immunity in cancer patients.
Our body contains trillions of microorganisms, which play a vital role in human health. Some microorganisms are "good" -- they are beneficial to our health. In contrast, some microorganisms are "bad" -- they may cause illness and health problems. A growing body of evidence suggests that bacteria in our gut affect patient responses to cancer immunotherapy.
A class of immunotherapy drugs is designed to target PD-1
, a checkpoint protein that appears to suppress the immune system during particular events. PD-1 plays a major role in tumor immune escape. Inhibition of PD-1 has been reported to have impressive antitumor responses. An anti-PD-1 immunotherapy, called pembrolizumab, has already been used to treat patients with inoperable or metastatic melanoma. But not all patients receiving the therapy respond well.
In the current study, Professor Gajewski's team investigated the relationship between the composition of the patients’ microbiome and the patient response to immunotherapy. Using gene sequencing, PCR, and other analytic methods, they examined stool samples from metastatic melanoma patients before immunotherapy. They identified that bacteria like Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium were more abundant in patients who responded to immunotherapy.
Bifidobacterium longum is an important microbe found in the human digestive tract, and its production of lactic acid helps lower the growth of pathogenic organisms. The bacterium Collinsella aerofaciens is found in the human gut and on the surface of the tongue, and this bacterium appears to reduce bloating. Enterococcus faecium is innocuous in the human intestine but may also be pathogenic.
Collectively, the results reveal that certain gut bacteria are associated with higher efficacy of anti-PD-1 immunotherapy in patients with metastatic melanoma. The composition of a cancer patient's microbiome influences antitumor immunity.
These findings provide one possible therapeutic strategy for cancer. That is using probiotics to improve the efficacy of immunotherapy. This concept needs to be further explored in animal preclinical models and next maybe in human clinical trials in cancer patients.
In conclusion, the study adds to the growing body of evidence that there is a link between gut bacteria and patient response to immunotherapy. With this knowledge, scientists may be able to develop more effective ways to enhance immunotherapy efficacy, improving the prognosis of cancer patients.