Cancer immunotherapy may lead to an increase in unexpected directions: bacteria residing inside tumor cells. In a new study published in Nature, researchers at the Weizmann Institute of Science and their colleagues have found that the immune system “sees” these bacteria and has shown that they can be used to stimulate an immune response against the eardrum.
The study may also help clarify the link between immunotherapy and the gut microbiome, explaining the findings of a previous study that the mosquito influences the success of immunotherapy.
Immunotherapy treatment in the last decade or so has achieved recovery rates from certain cancers, particularly malignant melanoma; but in melanoma, they still work in only about 40% of cases.
Professor Yardena Samuels from Weizmann’s Department of Molecular Cell Biology studies molecular “signs” – protein fragments, or peptides, on the surface of cells – that identify cancer cells as foreign and so on. they could be potential additional targets for immunotherapy. In the new study, she and her colleagues extended the study for new cancer signs to those bacteria that were known to colonize tumors.
Using techniques developed by the department’s colleague, Dr Ravid Straussman, who was one of the first to reveal the nature of the bacterial “guests” in cancer cells, Samuels and her team, led by the Dr. Shelly Kalaora and Adi Nagler (co-first co-authors), analyzed print samples from 17 metastatic melanoma tumors from nine patients. They obtained bacterial genomic images of these tumors and then applied a technique called HLA-peptidomics to identify tumor peptides that recognize the immune system.
The research was conducted in collaboration with Dr. Jennifer A. Wargo of Texas MD University Cancer Center, Houston, Texas; Professor Scott N. Peterson of the Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; Professor Eytan Ruppin of the National Cancer Institute, USA; Professor Arie Admon from the Technion – Israel Institute of Technology and other scientists.
HLA peptidomics study revealed nearly 300 peptides from 41 different bacteria on the surface of melanoma cells. The crucial new discovery was that the peptides were displayed on the surface of a cancer cell with HLA protein ratios – centers that are present on the organs of every cell in our body and are part of regulating the response waterproof.
One of the functions of the HLA is to issue an alarm against anything foreign by “displaying” foreign peptides to the immune system so that T cells can “see” immune cells. “Using HLA peptidomics, we were able to publish the tumor peptides exhibited by HLA in a neutral manner,” Kalaora says. “This approach has previously enabled us to identify tumor antigens that have shown promising results in clinical trials.”
It is unclear why cancer cells should perform this type of suicidal action: giving bacterial peptides to the immune system, which can respond by destroying these cells. But whatever the reason, the fact that malignant cells display these peptides in such a way reveals an entirely new type of interaction between the immune system and the tumor.
This finding provides a possible explanation for how the gut midge reacts to immunotherapy. Some of the bacteria identified by the team were known as gut microbes. The display of bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies may establish which bacterial peptides contribute to that immune response, allowing physicians predict the success of immunotherapy and adapt personal treatment. accordingly.
In addition, the fact that bacterial peptides on tumor cells can be seen by the immune system to enhance immunotherapy. “Many of these peptides have been shared with different metastases from the same patient or with tumors from different patients, which indicate their therapeutic potential and strong ability to produce immunity,” Nagler says.
In a series of follow-up experiments, Samuels and colleagues stimulated T cells from melanoma patients in a laboratory basin along with bacterial peptides derived from tumor cells of the same patient. The result: T cells were activated specifically towards the bacterial peptides.
Our findings suggest that bacterial peptides exhibited on tumor cells may be potential targets for immunotherapy. They can be used to help identify the tumor’s immune T cells more accurately, so that these cells can better attack the cancer. This approach can be used in the future in combination with existing immunotherapy drugs. “
Yardena Samuels, Prof.essor, Department of Molecular Cell Biology, Weizmann Institute of Science
Source:
Weizmann Institute of Science