Bacteria present in tumor cells can boost cancer immunotherapy

Cancer immunotherapy can be boosted by the unexpected direction of bacteria that are present in tumor cells.In a new study published in NatureResearchers at the Weizmann Institute of Science and their collaborators have discovered that the immune system “recognizes” these bacteria and has shown that they can be used to provoke an immune response against tumors.

This study may also help clarify the relationship between immunotherapy and the gut microbiota, explaining the findings of previous studies that the microbial flora influences the success of immunotherapy.

The last decade or so of immunotherapy treatment has dramatically improved recovery rates from certain cancers, especially malignant cancers. melanomaHowever, in melanoma, they still function in only about 40% of cases.

Professor Jardena Samuels of Weitzman’s Department of Molecular Cell Biology marks cancer cells as foreign and therefore molecular “labels” (protein fragments or peptides on the cell surface) that may serve as potential additional targets for immunotherapy. I am studying. In a new study, she and her colleagues extended the search for new cancer guideposts to bacteria known to colonize tumors.

Samuels and her team, led by Dr. Sherry Karaora and Dr. Adi Nagler, using a method developed by Dr. Rabbit Straussmann, a colleague in the department who first uncovered the nature of the bacterial “guest” in cancer cells. (Co-first author), tissue samples from 17 metastatic melanoma tumors from 9 patients were analyzed. They obtained the bacterial genome profiles of these tumors and applied an approach known as HLA peptide mix to identify tumor peptides that the immune system could recognize.

The study was conducted in collaboration with Dr. Jennifer A. Wago of the University of Texas MD Anderson Cancer Center (Houston, Texas). Professor Scott N. Peterson of the Sanford Burnham Pre-Beads Medical Discovery Institute in La Jolla, California. Professor Eytan Ruppin of the National Cancer Institute. Technion Professor Arie Admon-Israel Institute of Technology and other scientists.

HLA peptide mix analysis revealed approximately 300 peptides from 41 different bacteria on the surface of melanoma cells. An important new discovery was that peptides were displayed on the surface of cancer cells by the HLA protein complex, a complex that is present on the membranes of all cells in our body and plays a role in regulating the immune response.

One of the tasks of HLA is to warn about foreign peptides by “presenting” them to the immune system. T cells You can “see” them. “We were able to use HLA peptide mixes to reveal tumor peptides presented by HLA in an unbiased manner,” says Kalaora. “This method has already made it possible to identify tumor antigens that have shown promising results in clinical trials in the past.”

It is unclear why cancer cells need to perform this kind of seemingly suicide. You can respond by presenting bacterial peptides to the immune system and destroying these cells. But for whatever reason, the fact that malignant cells display these peptides in such a way reveals a whole new type of interaction between the immune system and the tumor.

This revelation provides a potential explanation for how the gut microbiota affects immunotherapy. Some of the bacteria identified by the team were known gut microbiota. Presentation of bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies will establish which bacterial peptides enhance the immune response and physicians predict the success of immunotherapy. And may allow individual treatments to be adjusted accordingly.

In addition, the fact that bacterial peptides on tumor cells appear to the immune system can be used to enhance immunotherapy. “Many of these peptides were shared by different metastases from the same patient or tumors from different patients, which means they have therapeutic potential and a strong ability to generate immune activation. Suggests, “says Nagler.

In a series of ongoing experiments, Samuels et al. Cultured T cells from a melanoma patient in a laboratory dish with bacterial peptides derived from tumor cells from the same patient. Results: T cells were specifically activated against bacterial peptides.

Our findings suggest that bacterial peptides presented to tumor cells may serve as potential targets for immunotherapy. They may be used to help immune T cells recognize tumors more accurately, so that these cells can launch a better attack on the cancer. This approach can be used in combination with existing immunotherapeutic agents in the future. “

Jardena Samuels, ProfessorProfessor, Department of Molecular Cell Biology, Weizmann Institute of Science