April 14, 2024

Researchers Provide Detailed Understanding of Immune Landscape in Cancer

A team of researchers has made a significant breakthrough in understanding immune responses in cancer, shedding light on the complex interplay of immune cells in tumors. The findings were published in the online issue of the scientific journal Cell on February 14, in a paper titled “Pan-cancer proteogenomics characterization of tumor immunity.” This groundbreaking study integrated data from over 1,000 tumors across 10 different types of cancer, using DNA, RNA, and proteomics analysis. The data was obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), a program supported by the National Cancer Institute.

The primary objective of this research was to gain a better understanding of the mechanisms underlying the functional impairment of immune response in tumors. By closely analyzing genes and proteins in tumor tissues, the team revealed various patterns of immune activation and suppression. “Our goal in unraveling these diverse immune subtypes is to help clinicians identify patient groups that are more responsive to immunotherapy,” says lead-author Dr. Pei Wang, Professor of Genetics and Genomic Sciences at Icahn Mount Sinai. “Revealing the specific pathways and cellular switches for each subtype can also inspire new treatment approaches.”

The researchers discovered that each type of immune response correlated with changes in gene functions, including modification, messaging, and protein production. By providing a comprehensive molecular profile of the immune response in cancer, this study is expected to facilitate the development of future immunotherapy strategies. “When we observe common immune responses and similar cell behavior patterns across different cancers within the same immune group, it suggests that certain treatments that boost the immune system could be effective for various types of cancer,” explains Dr. Wang.

One innovative aspect of this research is the deep phosphoproteomic data analysis performed on over 1,000 tumors. This data provides insights into 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 senior author Dr. Avi Ma’ayan, Professor of Pharmacological Sciences and Director of the Mount Sinai Center for Bioinformatics at Icahn Mount Sinai. “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.”

Additionally, a machine-learning tool applied to digital pathology images highlighted correlations between different types of immune responses and the presence of specific immune cells. This further improved the researchers’ understanding of the tumor microenvironment.

Moving forward, the investigators plan to validate their findings and leverage their 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.

The research team consisted of scientists from the Icahn School of Medicine at Mount Sinai, collaborating with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) 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 other esteemed institutions.

In line with this collaborative effort, CPTAC is currently conducting a proteogenomic study on the molecular mechanisms underlying responses to immune checkpoint treatments in melanoma patients. This research, along with the current study’s findings, holds immense potential for advancing cancer immunotherapy and improving patient outcomes.

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