News – Cancer immunotherapy can lead to an increase in unexpected directions: bacteria live 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 showing that the mosquito replicates the success of immunotherapy.
Immunotherapy treatment in the last decade or so has improved the recovery rates of patients from certain cancers, particularly malignant melanoma; however, they only work in about 40% of melanoma cases. Professor Yardena Samuels from Weizmann’s Department of Molecular Cell Biology examines molecular “signs” – protein fragments, or peptides, on the surface of the cells – that identify cancer cells as foreign and so could be potential targets for immunotherapy. In the new study, she and her colleagues expanded the study for signs of modern cancer leading to those bacteria that were known to colonize tumors.
Using techniques developed by her regional colleague, Dr. Ravid Straussman, who was one of the first to reveal the nature of bacterial “guests” in cancer cells, Professor Samuels and the team her, led by Dr. Shelly Kalaora and Adi Nagler (joint first co-authors), analyzed print samples from 17 metastatic melanoma tumors derived from nine patients. After obtaining bacterial genomic images of these tumors, they then applied an approach 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; Professor Scott N. Peterson of the Sanford Burnham Prebys Medical Discovery Institute, La Jolla; Professor Eytan Ruppin of the National Cancer Institute, Baltimore; 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 finding was that the peptides were exhibited on the surface of a cancer cell by HLA protein groups, which are present on the organs of every cell in our bodies and play a role in regulating the immune response . One of the functions of the HLA is to send out a warning device about anything foreign by “displaying” foreign peptides to the immune system so that immune T-cells can see them. “Using HLA peptidomics, we were able to publish the tumor peptides exhibited by HLA in a neutral manner,” Dr. Kalaora says. “This method has previously enabled us to identify tumor antigens that have shown promising results in clinical trials. ”
It is not clear why cancer cells should perform a suicidal action by presenting bacterial peptides to the immune system, which can respond by destroying the 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 were shared with different metastases from the same patient or with tumors from different patients, which indicate their therapeutic potential and strong ability to achieve immunity,” Nagler says.
In a series of follow-up experiments, Professor Samuels and her colleagues stimulated T cells from melanoma patients in a laboratory basin along with bacterial peptides derived from tumor cells from 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,” said Drs. Samuels. “They can be used to help immune T cells identify the tumor 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. “
Also participating in this research at the Weizmann Institute were Dr. Deborah Nejman, Dr. Michal Alon, Chaya Barbolin, Dr. Ronen Levy, Sophie Trabish, Dr. Leore Geller, Polina Greenberg, Gal Yagel, Dr. Aviyah Peri, and Lior Roitman from the Department of Molecular Cell Biology; Yuval Bussi, Dr. Adina Weinberger, Maya Lotan-Pompan, and Professor Eran Segal from the Department of Computer Science and Applied Mathematics and the Department of Molecular Cell Biology; Professor Ron Rotkopf and Ofra Golani from the Department of Basic Resources Life Sciences; Dr. Tali Dadosh and Dr. Smadar Levin-Zaidman from the Department of Chemical Research Support; Dr. Garold Fuks from the Department of Integrated Systems Physics; and Dr Raya Eilam from the Department of Veterinary Resources.
Professor Yardena Samuels ’research is supported by the EKARD Institute for Cancer Diagnosis Research; Weizmann-Brazil Tumor Bank; Moross Integrated Cancer Center; the laboratory in the name of the MEH Fund founded by Margot and Ernst Hamburger; Green Family Charitable Foundation; Wagner-Braunsberg Family Melanoma Research Fund; Jean-Jacques Brunschwig Fund for Molecular Cancer Genetics; Property of Erica Drake; Miel de Botton; the Rising Tide Foundation; the areas Fundación Ramón; Hanna and Dr. Cancer Research Fund Ludwik Wallach; Jacques Asseoff Trust; the estate of Adrian Finer; Mady Dukler estate; Karl-Johan Persson; and the estate of Malka Moskowitz. Professor Samuels is the chairman of the Knell Family Professional Chair.
The Weizmann Institute of Science in Rehovot, Israel, is one of the top multidisciplinary research centers in the world. The Institute’s strong 3,800 scientific community is engaged in research addressing critical problems in medicine and health, energy, technology, agriculture and the environment. Unique young scientists from around the world take advanced degrees at the Feinberg Graduate School at the Weizmann Institute. The discoveries and theories of Weizmann Institute scientists have had a profound impact on the wider scientific community, as well as the quality of life of millions of people around the world.