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Cancer cells co-opt immune response to escape destruction
Date:12/18/2012

Researchers at the University of California, San Diego School of Medicine report that tumor cells use stress signals to subvert responding immune cells, exploiting them to actually boost conditions beneficial to cancer growth.

The findings are published in the December 18 online issue of the journal PLOS ONE.

Lead author Navin R. Mahadevan, a graduate student in the Laboratory of Immunology at the UC San Diego Moores Cancer Center, and colleagues found that tumor cells manipulate a fundamental cellular mechanism called unfolded protein response (UPR). In all cells, UPR is used to maintain homeostasis, or equilibrium, in the endoplasmic reticulum (ER) the cell's protein-making factory. When, for a variety of reasons, a cell is subjected to overwork, ER stress occurs and a compensatory UPR is triggered.

"The goal is to understand how ER stress is transmitted and how this is amplified by receiver cells to attack vulnerable aspects of the immune system," said principal investigator Maurizio Zanetti, MD, who heads the Laboratory of Immunology and is director of Tumor Immunology at the Center for Immunity, Infection and Inflammation at UC San Diego.

"These findings suggest that the tumor UPR should be a target of therapy, not only for its intrinsic function in promoting tumor adaption and survival, but now for its external role in subverting the anti-tumor immune response."

When a UPR response is triggered, one of two things can happen. Either UPR restores homeostasis by slowing cellular processes and synthesizing chaperone molecules to ease the burden on the endoplasmic reticulum or it decides homeostasis can't be restored and the cell is better off dying. The latter is called apoptosis, or programmed cell death.

In research published last year, Zanetti and colleagues found that the UPR is transmissible: It can travel from one cell to another. In normal cells, ER stress is transient with the UPR u
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Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert  

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