Study Helps Clarify Connection Between Microbiome and Immunotherapy

In a new study published in Nature, researchers at the Weizmann Institute of Science and their collaborators have discovered that the immune system identifies bacteria that reside within tumor cells, and show they can be harnessed to provoke an immune reaction against the tumor. The study may also help clarify the connection between immunotherapy and the gut microbiome, explaining the findings of previous research that the microbiome affects the success of immunotherapy.

The team analyzed tissue samples from 17 metastatic melanoma tumors derived from nine patients. They obtained bacterial genomic profiles of these tumors and then applied an approach known as HLA-peptidomics to identify tumor peptides that can be recognized by the immune system. Their analysis revealed nearly 300 peptides from 41 different bacteria on the surface of the melanoma cells. "Using HLA peptidomics, we were able to reveal the HLA-presented peptides of the tumor in an unbiased manner," co-author Shelly Kalaora says. "This method has already enabled us in the past to identify tumor antigens that have shown promising results in clinical trials."

In a series of continuing experiments, the researchers incubated T cells from melanoma patients in a laboratory dish together with bacterial peptides derived from tumor cells of the same patient. They found that the T cells were activated specifically toward the bacterial peptides. "Our findings suggest that bacterial peptides presented on tumor cells can serve as potential targets for immunotherapy," co-author Yardena Samuels said. "They may be exploited to help immune T cells recognize the tumor with greater precision, so that these cells can mount a better attack against the cancer. This approach can in the future be used in combination with existing immunotherapy drugs."