Home Medizin Phosphoproteomische Profilierung enthüllt das komplexe Zusammenspiel von Immunzellen in Tumoren

Phosphoproteomische Profilierung enthüllt das komplexe Zusammenspiel von Immunzellen in Tumoren

von NFI Redaktion

Researchers at the Icahn School of Medicine at Mount Sinai, in collaboration with the National Institutes of Health’s Clinical Proteomic Tumor Analysis Consortium, the MD Anderson Cancer Center at the University of Texas, the Sylvester Comprehensive Cancer Center at the Miller School of Medicine at the University of Miami, and others, have unveiled a detailed understanding of immune responses in cancer, marking a significant breakthrough in this field. The results were published in the online edition on February 14th Cell [DOI: 10.1016/j.cell.2024.01.027].

The study uses data from over 1,000 tumors in 10 different cancer types and is the first to integrate DNA, RNA, and proteomics (the study of proteins), uncovering the complex interplay of immune cells in tumors. The data comes from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), a National Cancer Institute program.

„Our goal was to enhance our understanding of the mechanisms underlying the functional impairment of the immune response in tumors. By closely examining genes and proteins in tumor tissue, we discovered different patterns in the activation and suppression of the immune system. Our aim in elucidating these various immune subtypes is to help physicians identify groups of patients who respond better to immunotherapy. Revealing the specific signaling pathways and cellular switches for each subtype can also open up new and creative ways for treatment development,“

Pei Wang, PhD, Professor of Genetics and Genomic Sciences at Icahn Mount Sinai and lead author of the article.

„Every type of immune response was associated with changes in gene functions, such as how genes are altered, what messages they send, and which proteins they produce. By providing a comprehensive molecular fingerprint of the immune response in cancer, this study is expected to help facilitate the development of future immunotherapy strategies,“ says Francesca Petralia, PhD, Assistant Professor of Genetics and Genomic Sciences at Icahn Mount Sinai and co-author of the paper.

An important finding was that of the seven subtypes identified through advanced statistical models, five encompassed tumors from 10 different cancer types, indicating shared immune reactions among these tumors.

„When we see common immune reactions and similar patterns in cell behavior in different cancer types within the same immune group, it suggests that specific treatments that enhance the immune system might work well for many types of cancer,“ says Dr. Wang.

A new aspect of the research arises from the detailed phosphoproteomic data generated for over 1,000 tumors. Through this data, researchers can see how proteins are altered. „By profiling the phosphoproteome of over 1,000 cancer tumors, we were able to computationally discover a series of important new drug targets,“ says Avi Ma’ayan, PhD, Professor of Pharmacological Sciences and Director of the Mount Sinai Center for Bioinformatics at the Icahn Mount Sinai and senior author of the article. „By selectively targeting kinases with small molecules or other agents, we may be able to potentially transform tumors that don’t respond to immunotherapies into ones that respond better to immunotherapy.“

In the course of the research, a machine learning tool applied to digital pathology images also showed correlations between different types of immune responses and the presence of certain immune cells, improving the understanding of the environment in and around tumors.

Next, the researchers plan to further validate their findings and leverage insights from ongoing clinical studies focused on immunotherapies. These efforts aim to streamline the development of biomarker panels for treatment responses and identify improved treatment strategies. Within CPTAC, joint efforts are underway, including a proteogenomic study on the molecular mechanisms underlying responses to immune checkpoint treatments in melanoma patients.


Mount Sinai Health System

Journal reference:

Petralia, F., et al. (2024) Pan-Cancer Proteogenomic Characterization of Tumor Immunity. Cell. doi.org/10.1016/j.cell.2024.01.027.

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