While experts have believed that the gut microbiome may be critical in regulating how the immune system fights tumors in cancer patients, the mechanisms underlying this relationship have remained unclear. For the first time, an international team of 40 scientists led by Sanford Burnham Prebys (SBP) has demonstrated a causal link between the gut microbiome and the immune system’s ability to fight cancer.
The researchers identified a combination of 11 bacterial strains that activated the immune system and slowed the growth of melanoma in mice. The experts also determined that the unfolded protein response (UPR), a cellular signaling pathway called which maintains protein health, plays an important role in the body’s response to cancer treatment known as immune checkpoint therapy.
“Immunotherapies have extended the lives of many cancer patients. However, the incredible effects we are seeing today are only the tip of the iceberg. By studying mechanisms of treatment response versus resistance, we can eventually expand the number of people who benefit from immunotherapy,” said study co-author Dr. Thomas Gajewski.
“This study provides an important step toward this goal. The investigators have pinpointed the UPR as an important link between the gut microbiota and anti-tumor immunity. Given previous work indicating a causal role for the host microbiota in the efficacy of checkpoint blockade immunotherapy, this additional mechanistic insight should help select patients who will respond to treatment and also help to guide new therapeutic development.”
According to the American Cancer Society, metastatic melanoma remains the deadliest form of skin cancer. Immune checkpoint inhibitors, which “release the brakes” of the body’s immune system to launch an efficient tumor attack, do not work for everyone. Even when used as part of combination therapy, immune checkpoint inhibitors only benefit about half of patients.
A growing collection of research supports the role of the gut microbiome in effective immunotherapy. Studies have shown that antibiotics and select probiotics reduce the effectiveness of treatment, while certain bacterial strains can improve the effectiveness of the treatment. The current study is providing new insight into these observations.
“Our study establishes a formal link between the microbiome and anti-tumor immunity and points to the role of the UPR in this process, answering a long-sought question for the field,” said senior author Dr. Ze’ev Ronai. “These results also identify a collection of bacterial strains that could turn on anti-tumor immunity and biomarkers that could be used to stratify people with melanoma for treatment with select checkpoint inhibitors.”
The research is published in the journal Nature Communications.