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Jumbled chromosomes may dampen the immune response to tumors

Date:
January 19, 2017
Source:
American Association for the Advancement of Science
Summary:
How well a tumor responds to immunotherapy may depend in part on whether its chromosomes are intact or in a state of disarray, a new study reports. The finding could help doctors better pinpoint which cancer patients would benefit from immunotherapy.
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How well a tumor responds to immunotherapy may depend in part on whether its chromosomes are intact or in a state of disarray, a new study reports. The finding could help doctors better pinpoint which cancer patients would benefit from immunotherapy.

Cancer immunotherapy can produce durable clinical responses, but only in a subset of patients. Why certain patients benefit more than others is still unclear. Many tumors are characterized by "aneuploidy," meaning they display an abnormal number of chromosomes and chromosomal segments.

A high degree of aneuploidy is a feature of high-grade tumors and is associated with poor prognosis.

Here, Teresa Davoli and colleagues examined data from over 5,000 tumor samples representing 12 cancer types from The Cancer Genome Atlas (TCGA) project. The team found that high-aneuploidy tumors had increased expression of genes implicated in DNA replication, cell cycle, mitosis, and chromosome maintenance, yet decreased expression of genes characteristic of the infiltrating immune cells responsible for tumor destruction.

In a retrospective analysis of clinical trial data, they found that melanoma patients with highly aneuploid tumors were less likely to benefit from immune checkpoint blockade therapy than patients whose tumors showed fewer chromosomal disruptions. These findings are highlighted in a Perspective by Maurizio Zanetti.


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Materials provided by American Association for the Advancement of Science. Note: Content may be edited for style and length.


Journal Reference:

  1. Teresa Davoli, Hajime Uno, Eric C. Wooten, Stephen J. Elledge. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science, 2017; 355 (6322): eaaf8399 DOI: 10.1126/science.aaf8399

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American Association for the Advancement of Science. "Jumbled chromosomes may dampen the immune response to tumors." ScienceDaily. ScienceDaily, 19 January 2017. <www.sciencedaily.com/releases/2017/01/170119143325.htm>.
American Association for the Advancement of Science. (2017, January 19). Jumbled chromosomes may dampen the immune response to tumors. ScienceDaily. Retrieved May 25, 2017 from www.sciencedaily.com/releases/2017/01/170119143325.htm
American Association for the Advancement of Science. "Jumbled chromosomes may dampen the immune response to tumors." ScienceDaily. www.sciencedaily.com/releases/2017/01/170119143325.htm (accessed May 25, 2017).

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