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Researchers from the Icahn School of Medicine at Mount Sinai, in collaboration with the National Institutes of Health’s Clinical Proteomic Tumor Analysis Consortium, the University of Texas MD Anderson Cancer Center, the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, and Others, have unveiled a detailed understanding of the immune response in cancer, leading to a significant advance in the field. The results were published in the February 14 online issue. Sale.

Using data from more than 1,000 tumors in 10 different cancers, the study is the first to integrate DNA, RNA, and proteomics (the study of proteins) to reveal the complex interactions of immune cells in tumors. It turns out. The data comes from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), a program run by the National Cancer Institute.

“We wanted to improve our understanding of the mechanisms underlying functional impairment of the immune response in tumors. By closely examining genes and proteins in tumor tissues, we discovered different patterns of immune activation and suppression. ” says P. Wang, Ph.D., prof. Icahn of Genetics and Genomic Sciences at Mount Sinai, and lead corresponding author on the paper. “Our goal in unraveling these diverse immune subtypes is to help clinicians identify patient groups that are more responsive to immunotherapy. Revealing the pathways and cellular switches specific to each subtype will help tailor treatments.” can also give rise to new and creative ways of

“Each type of immune response was linked to changes in gene function, such as how genes are turned on, the messages they send, and the proteins they produce. Future immunotherapy strategies facilitate development,” says Francesca Petralia, PhD, Icahn assistant professor of genetics and genomic sciences at Mount Sinai and co-corresponding author on the paper.

A key finding was that five of the seven subtypes identified by the advanced statistical models included tumors from ten different cancer types, suggesting a common immune response among these tumors.

“When we see common immune responses and similar patterns in the behavior of cells in different cancers within the same immune group, it indicates that certain treatments that boost the immune system may be effective in many cancers,” says Dr. Wang. Can work better for types.”

A new aspect of research emerges from deep phosphoproteomic data generated for more than 1,000 tumors. This data allows researchers to see how proteins are modified. “With phosphoproteomic profiling of more than 1,000 pan-cancer tumors, we were able to computationally discover a set of key drug targets,” said Avi Ma’ayan, PhD, Professor, Pharmacological Sciences, Mount Sinai Center for Biomedical Sciences. Director of Informatics says. Icahn Mount Sinai, and a senior author of the paper. “By targeting selected kinases with small molecules or other means, we can convert tumors with improved immune therapy response to tumors unresponsive to immunotherapies.”

As part of the research, a machine learning tool applied to digital pathology images also demonstrated correlations between different types of immune response and the presence of certain immune cells, leading to an understanding of the environment in and around the tumor. Increases.

After that, the investigators plan to further validate their findings and leverage insights into ongoing clinical studies focused on immunotherapies. The goal of this effort is to streamline the development of biomarker panels for treatment response and identify better treatment strategies. Collaborative efforts are ongoing within CPTAC, including proteogenomic studies on the molecular mechanisms underlying response to immune checkpoint therapy in melanoma patients.

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