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Researchers characterize the immune landscape in cancer

Findings could pave the way for the development of new therapeutic strategies

Date:
February 14, 2024
Source:
The Mount Sinai Hospital / Mount Sinai School of Medicine
Summary:
Researchers have unveiled a detailed understanding of immune responses in cancer, marking a significant development in the field. Utilizing data from more than 1,000 tumors across 10 different cancers, the study is the first to integrate DNA, RNA, and proteomics (the study of proteins), revealing the complex interplay of immune cells in tumors.
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Researchers from the Icahn School of Medicine at Mount Sinai, in collaboration with the Clinical Proteomic Tumor Analysis Consortium of the National Institutes of Health, The University of Texas MD Anderson Cancer Center, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, and others, have unveiled a detailed understanding of immune responses in cancer, marking a significant development in the field. The findings were published in the February 14 online issue of Cell.

Utilizing data from more than 1,000 tumors across 10 different cancers, the study is the first to integrate DNA, RNA, and proteomics (the study of proteins), revealing the complex interplay of immune cells in tumors. The data came from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), a program under the National Cancer Institute.

"We aimed to improve our understanding of the mechanisms underlying the functional impairment of immune response in tumors. By closely examining genes and proteins in the tumor tissues, we discovered various patterns in immune activation and suppression," says Pei Wang, PhD, Professor of Genetics and Genomic Sciences at Icahn Mount Sinai, and the lead-corresponding author on the paper. "Our goal in unraveling these diverse immune subtypes is to help clinicians identify patient groups more responsive to immunotherapy. Revealing the specific pathways and cellular switches for each subtype can also spark new and creative ways to develop treatments."

"Each type of immune response was linked to changes in gene functions, such as how genes are modified, the messages they send, and the proteins they produce. By providing a comprehensive molecular fingerprint of the immune response in cancer, this study is expected to facilitate the development of future immunotherapy strategies," says Francesca Petralia, PhD, Assistant Professor of Genetics and Genomic Sciences at Icahn Mount Sinai, and co-corresponding author on the paper.

A key finding was that among seven subtypes identified through advanced statistical models, five included tumors from ten different types of cancer, suggesting shared immune responses across these tumors.

"When we see common immune responses and similar patterns in the way cells behave across various cancers within the same immune group, it hints that certain treatments that boost the immune system could work well for many types of cancer," says Dr. Wang.

A novel aspect of the research stems from the 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 novel drug targets," says Avi Ma'ayan, PhD, Professor, Pharmacological Sciences, Director of the Mount Sinai Center for Bioinformatics at Icahn Mount Sinai, and a senior author of the paper. "By targeting selected kinases with small molecules or other means, we may be able to convert tumors not responding to immunotherapies into tumors with better immune-therapy response."

As part of the research, a machine-learning tool applied to digital pathology images also demonstrated correlations between different types of immune responses and the presence of certain immune cells, enhancing understanding of the environment in and around tumors.

Next, the investigators plan to validate their findings further and leverage insights in ongoing clinical studies focused on immunotherapies. This effort aims to streamline the development of biomarker panels for treatment responses and identify enhanced treatment strategies. Collaborative efforts within CPTAC are underway, including a proteogenomic study on molecular mechanisms underlying responses to immune checkpoint treatments in melanoma patients.


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Materials provided by The Mount Sinai Hospital / Mount Sinai School of Medicine. Note: Content may be edited for style and length.


Journal Reference:

  1. Francesca Petralia, Weiping Ma, Tomer M. Yaron, Francesca Pia Caruso, Nicole Tignor, Joshua M. Wang, Daniel Charytonowicz, Jared L. Johnson, Emily M. Huntsman, Giacomo B. Marino, Anna Calinawan, John Erol Evangelista, Myvizhi Esai Selvan, Shrabanti Chowdhury, Dmitry Rykunov, Azra Krek, Xiaoyu Song, Berk Turhan, Karen E. Christianson, David A. Lewis, Eden Z. Deng, Daniel J.B. Clarke, Jeffrey R. Whiteaker, Jacob J. Kennedy, Lei Zhao, Rossana Lazcano Segura, Harsh Batra, Maria Gabriela Raso, Edwin Roger Parra, Rama Soundararajan, Ximing Tang, Yize Li, Xinpei Yi, Shankha Satpathy, Ying Wang, Maciej Wiznerowicz, Tania J. González-Robles, Antonio Iavarone, Sara J.C. Gosline, Boris Reva, Ana I. Robles, Alexey I. Nesvizhskii, D.R. Mani, Michael A. Gillette, Robert J. Klein, Marcin Cieslik, Bing Zhang, Amanda G. Paulovich, Robert Sebra, Zeynep H. Gümüş, Galen Hostetter, David Fenyö, Gilbert S. Omenn, Lewis C. Cantley, Avi Ma'ayan, Alexander J. Lazar, Michele Ceccarelli, Pei Wang, Jennifer Abelin, François Aguet, Yo Akiyama, Eunkyung An, Shankara Anand, Meenakshi Anurag, Özgün Babur, Jasmin Bavarva, Chet Birger, Michael J. Birrer, Song Cao, Steven A. Carr, Daniel W. Chan, Arul M. Chinnaiyan, Hanbyul Cho, Karl Clauser, Antonio Colaprico, Daniel Cui Zhou, Felipe da Veiga Leprevost, Corbin Day, Saravana M. Dhanasekaran, Li Ding, Marcin J. Domagalski, Yongchao Dou, Brian J. Druker, Nathan Edwards, Matthew J. Ellis, Steven M. Foltz, Alicia Francis, Yifat Geffen, Gad Getz, David I. Heiman, Runyu Hong, Yingwei Hu, Chen Huang, Eric J. Jaehnig, Scott D. Jewell, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A. Ketchum, Iga Kolodziejczak, Karsten Krug, Chandan Kumar-Sinha, Jonathan T. Lei, Wen-Wei Liang, Yuxing Liao, Caleb M. Lindgren, Tao Liu, Wenke Liu, Jason McDermott, Wilson McKerrow, Mehdi Mesri, Michael Brodie Mumphrey, Chelsea J. Newton, Robert Oldroyd, Samuel H. Payne, Pietro Pugliese, Karin D. Rodland, Fernanda Martins Rodrigues, Kelly V. Ruggles, Sara R. Savage, Eric E. Schadt, Michael Schnaubelt, Tobias Schraink, Stephan Schürer, Zhiao Shi, Richard D. Smith, Feng Song, Yizhe Song, Vasileios Stathias, Erik P. Storrs, Jimin Tan, Nadezhda V. Terekhanova, Ratna R. Thangudu, Mathangi Thiagarajan, Liang-Bo Wang, Bo Wen, Yige Wu, Matthew A. Wyczalkowski, Lijun Yao, Qing Kay Li, Hui Zhang, Qing Zhang, Xu Zhang, Zhen Zhang. Pan-cancer proteogenomics characterization of tumor immunity. Cell, 2024; DOI: 10.1016/j.cell.2024.01.027

Cite This Page:

The Mount Sinai Hospital / Mount Sinai School of Medicine. "Researchers characterize the immune landscape in cancer." ScienceDaily. ScienceDaily, 14 February 2024. <www.sciencedaily.com/releases/2024/02/240214122556.htm>.
The Mount Sinai Hospital / Mount Sinai School of Medicine. (2024, February 14). Researchers characterize the immune landscape in cancer. ScienceDaily. Retrieved April 15, 2024 from www.sciencedaily.com/releases/2024/02/240214122556.htm
The Mount Sinai Hospital / Mount Sinai School of Medicine. "Researchers characterize the immune landscape in cancer." ScienceDaily. www.sciencedaily.com/releases/2024/02/240214122556.htm (accessed April 15, 2024).

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