TAMPA, Fla. – The prognosis of ovarian cancer is poor, with an estimated five-year survival rate of just 40% for advanced disease, the rate at which most ovarian carcinomas are diagnosed. These adverse effects are partly due to the lack of effective treatments for advanced disease and relapse. Immunotherapies promise many types of cancer; however, studies have shown that patients with ovarian cancer do not have strong responses to the available drugs. In a new article published in Nature, Researchers at the Moffitt Cancer Center show why some ovarian cancer patients progress better than others and suggest possible approaches to improve patient outcomes .
Immunotherapeutic drugs activate T cells, a type of immune cell, to provide immunity against tumor cells. Immunotherapies are approved to treat several different types of cancer and have significantly changed the level of care and improved patient outcomes. However, in ovarian cancer, clinical studies continued to use immunotherapies that aimed to stimulate T cells to moderate response levels. Studies have suggested that cancer patients with a higher presence of other immune cells, such as plasma and B memory cells, may respond better to immunotherapies, but it is unclear how these cell types induce outcomes. better. The Moffitt researchers wanted to determine whether antibodies secreted by these cells are associated with better outcomes and to evaluate how these cells contribute to the immune response against tumors. no spoon against ovarian cancer.
The researchers analyzed a panel of 534 samples from ovarian cancer patients and found that patients with higher infiltration of B cells or B cell plasma cells had better outcomes. It is a type of immune cell. are B cells that make antibodies and express one of five types of B cell receptors on their surface: IgM, IgD, IgG, IgE or IgA. These isotypes regulate various B cell signaling and control B cell processes.
The surprise came when Moffitt’s team found, after further analysis of the samples, that the antibodies produced by B cells and plasma contained the bulk of the IgA subtype, followed by IgG.
“We found that the presence of IgA regulated downstream signaling pathways of the ovarian cancer cells. In particular, IgA blocked the RAS signaling pathway, which is known to contribute to the development of ovarian cancer,” he said. Jose Conejo-Garcia, MD, Ph .D., Chairman of the Moffitt Department of Psychiatry.
This inhibition of RAS induced tumor cell proliferation to T cell-mediated cell killing, induced by both modern CAR T cells and tumor-infiltrating lymphocytes. The team also assessed that IgA and IgG secreted by the B cells recognizing the surface markers of specific ovarian tumor cells and stimulating other immune cells called myeloid cells to target ovarian cancer cells for destruction.
These data provide new insights into how parts of the immune system regulate ovarian cancer progression and offer new opportunities to develop better targeted producers. This includes a repertoire of tumor-derived antibodies that can be used effectively as novel immunotherapeutic agents. In addition, the study provides a mechanistic rationale for integrated antibody responses in the development of novel immunotherapies, which to date have been based on T-cell-centric approaches.
“The findings show that immunotherapies that stimulate both coordinated B and T cell responses against ovarian cancer, an immunogenic disease that is currently against check-in immunosuppressants, appear to be show superior therapeutic benefit, ”said Subir Biswas, Ph.D., first author and postdoctoral. one in the Conejo-Garcia laboratory.
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The latter study paves the way for the use of antibodies different from IgG as immunotherapeutic agents for at least tumors that currently resist normal immune check inhibition.
This study was supported by the National Institutes of Health (P30CA076292, R01CA240434, R01CA157664, R01CA124515, T32CA009140, U01CA200495) and the American Cancer Society (PF-18-041-1-LIB).
About Moffitt Cancer Center
Moffitt is specifically for one life-saving mission: contributing to cancer prevention and treatment. The Tampa-based facility is one of only 51 Comprehensive Cancer Centers designated by the National Cancer Institute, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt is the No. 11 cancer hospital and has been ranked nationally by U.S. News & World Report since 1999. Moffitt’s experienced nursing staff is recognized by the Magnet®-certified American Nurses Certification Center, the highest reputation. With more than 7,000 team members, Moffitt has an economic impact of $ 2.4 billion in the state. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the trend on Facebook, Twitter, Instagram and YouTube.
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