Cell: new research helps identify invasive breast cancer that responds to immunotherapy

November 20, 2019 / Biovalley BIOON / - -- the United States Food and Drug Administration (FDA) recently approved the combination of immunotherapy drugs and chemotherapy drugs for the treatment of triple negative breast cancer, but not all cases of this invasive breast cancer respond in clinical research In a new study, researchers from institutions such as the University of North Carolina in the United States found biological clues that could be used to help identify invasive breast cancer that responds to drugs that activate the immune system against cancer Their findings were obtained by studying mice and analyzing data from six clinical trials If confirmed in future studies, these new insights may help guide patients to the right treatment and keep them away from ineffective treatment It could also lead to a way for drugs to work in cancers that initially did not respond The relevant research results are published in the cell Journal on November 14, 2019, and the paper title is "B cells and t spherical helper cells mediate response to checkpoint inhibitors in high residence burden mouse models of breast cancer" Picture from cell, 2019, DOI: 10.1016/j.cell.2019.10.028 "Potentially, we will use a new biomarker to determine which triple negative breast cancer patients should receive immunotherapy," said Dr Charles M perou, co-author of the paper and at the University of North Carolina's lennberg comprehensive cancer center Three kinds of receptors, estrogen receptor, progesterone receptor and HER2 / erbB2 protein, are absent in three negative breast cancer patients In the United States, it accounts for about 12% of invasive breast cancer cases and is more likely to affect young women, black women and people with BRCA1 mutations If the treatment options targeting these three receptors are not available, doctors will usually use chemotherapy drugs, which will indiscriminately attack the rapidly dividing cells in the body, which may be effective for many triple negative breast cancer patients In 2018, the FDA approved the combination of immunotherapy drug atzolizumab and chemotherapy drugs for the treatment of triple negative breast cancer patients with metastasis (i.e cancer cells spread from the breast) This is the first time the FDA has approved a treatment containing immunotherapy drugs for breast cancer Atjumab is an immunosuppressive checkpoint inhibitor As a kind of immunotherapy drugs, immunosuppressive checkpoint inhibitors can remove the inhibition of cancer cells on T cells, so that these T cells can find and attack cancer cells This kind of immunotherapy drugs has breakthrough significance for patients with advanced melanoma (the most fatal skin cancer) and other cancers In October last year, a study published in the Journal of New England Journal of Medicine reported that the combination of atrazine monotherapy and chemotherapy could prolong the progression free survival of some PD-L1 positive triple negative breast cancer patients (NEJM, 2018, DOI: 10.1056 / nejmoa1809615) 41% of triple negative breast cancer patients are PD-L1 positive, but not all triple negative breast cancer patients respond to this combination therapy To find out why some triple negative breast cancers respond to immunotherapy while others do not, perou and his colleagues built a variety of mouse models of triple negative breast cancer to determine the biological characteristics of triple negative breast cancer that respond to treatment In order to answer this question, these mouse models have to respond to immunotherapy, which the existing mouse models cannot do They genetically modified the existing mouse models to contain a large number of "tumor antigens" (abnormal proteins in tumors that trigger the immune system), so these genetically modified mouse models have a high response to immunotherapy They then used genetic tools to analyze the biological characteristics of triple negative breast cancer that responded to immunotherapy and revealed the "signature" of the response using gene expression data As a biomarker, this feature reveals the clues leading to the role of immunotherapy: Patients with cancer respond to treatment have a coordinated immune response to cancer, which involves a variety of immune cells, including two T cells, which can directly attack and kill tumors; B cells, which can produce antibodies that may attack tumors The researchers also found that gene expression patterns can be used to identify immunotherapeutic responses in three negative breast cancer mice and analyze data from human clinical trials They point out that they may use gene expression patterns to identify breast cancer that responds to chemotherapy, HER2 positive breast cancer that responds to trastuzumab, and, importantly, human melanoma that responds to immunotherapy "There are many types of immune cells that need to work together to produce an effective immune response, and this biomarker can show when B cells and T cells work together," perou said And as long as we see that, it can predict better responses - whether it's immunotherapy for melanoma, HER2 targeted therapy for breast cancer patients, or chemotherapy for triple negative breast cancer patients " They believe the finding could identify both patients who benefit from immunotherapy and those who do not Perou added that they also hope to use their findings to develop new ways to enhance therapeutic response Dr Dan hollern, the first author of the paper and a postdoctoral researcher at the University of North Carolina's leenberg comprehensive cancer center, said: "our current research work is to find ways to use B cells to improve treatment plans and programs for breast cancer patients We absolutely need to study ways to activate B cells more effectively " The researchers said they also plan to study the biomarker in further studies in order to continue to assess the characteristics of treatment response in triple negative breast cancer patients undergoing this immunotherapy combination (bio.com) reference: 1 Daniel P hollern et al B cells and T cellular helper cells mediate response to checkpoint inhibitors in high mutation burden mouse models of burst cancer Cell, 2019, DOI: 10.1016/j.cell.2019.10.028 2 Findings could help identify which aggressive burst cancers will respond to immediate treatments https://unclineberger.org/news-archives/predicting-triple-negative-breast-cancer-response-to-immunotherapy/