Navigation Links
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 usually restoring normal function. But cancer cells thrive in an environment in which low oxygen and scarce nutrients, such as glucose, induce continuous ER stress. For them, a sustained ER stress response "offers a survival advantage by promoting cancer cell adaptation, continued growth, and inflammation that is more damaging than healing," Zanetti said.

In the latest study, the scientists found that the transmissible ER stress response (TERS), which emanates from tumor cells experiencing ER stress, alters immune cells in such a way that they no longer function to help fight off cancer. Normally dendritic cells the sentinels and information couriers of the immune system train T cells (the immune system's enforcers) to specifically kill foreign entities. In the case of cancer, however, T cells are unable to properly eliminate tumor cells confounding efforts to develop more effective cancer treatments. The new findings implicate TERS as cancer's siren call. It brainwashes dendritic cells so that they ineffectively communicate with T cells, reducing anti-tumor immunity while increasing tumor growth.

"This is one of the hot topics of contemporary immunology," said Mahadevan. "Our paper shows that TERS and by inference ER stress in tumor cells has the ability to negatively affect the sanctuary of the immune response."

Zanetti said the research further elucidates the fundamental processes that tumor cells use or abuse to manipulate their local microenvironment to promote their survival and growth. And it points to an area of drug development the pharmaceutical industry will likely focus on over the next decade.

Targeting the UPR, he said, may also help improve efficacy of long-sought cancer vaccines which have thus far been hampered by the ability of cancer cells to subvert the immune response, perhaps through mechanisms like TERS.


'/>"/>

Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert  

Related medicine news :

1. World Trade Center rescue, recovery workers have had increased incidence of certain types of cancer
2. With Testicular Cancer, CT Scan Benefit May Beat Risks
3. Researchers find model system to study promising cancer drug
4. Spread of cancer cells may be slowed by targeting of protein
5. US Drug Watchdog Now Urges Users Of The Diabetes Drug Called Actos To Call The Johnson Law Group if They Have Developed Bladder Cancer-Time Is Of The Essence
6. Malecare Announces a New LGBT Cancer Survivor Support Group in Indianapolis Indiana
7. Immediate health risk must be weighed against radiation-induced cancer risk
8. Mayo Clinic researchers identify enzyme linked to prostate cancer
9. New technology may enable earlier cancer diagnosis
10. CWRU School of Medicine researchers discover new molecule linked to late-stage breast cancer
11. PRT versus IMRT toxicity in Medicare beneficiaries with prostate cancer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Cancer cells co-opt immune response to escape destruction
(Date:7/25/2017)... ... July 25, 2017 , ... SureVest Insurance Group, ... to communities across North Carolina, is launching a charity event in conjunction with ... for the ongoing fight against bladder cancer. , The Bladder Cancer Advocacy Network ...
(Date:7/25/2017)... (PRWEB) , ... July 25, 2017 , ... ... Health, as medical director. Dr. Negrette has more than a decade of experience ... has worked closely with individuals fighting addictions, eating disorders, psychotic and manic conditions, ...
(Date:7/24/2017)... ... , ... Engineers at the University of Maryland have invented an entirely new ... energy that the body uses. , In ordinary batteries the electrical energy, or ... of the battery is generated by moving positive ions from one end to the ...
(Date:7/24/2017)... ... 2017 , ... Cosmetic Town, an online plastic surgery information community, announces a ... a daily basis. , The new video series will feature board-certified doctors explaining ... practices. , When asked about the new video series, the senior editor of ...
(Date:7/24/2017)... ... July 24, 2017 , ... ... scholarship awards to be awarded annually to and divided between two full-time university ... bringing awareness to Amazonian plant medicine. To apply for the scholarship, students are ...
Breaking Medicine News(10 mins):
(Date:7/15/2017)... Enterin Inc., a Philadelphia -based ... today announced the completion of a $12.7 million Series A ... as well as the participation of existing investors. ... the support of New Ventures III and our current investors, ... the potential of our platform technology to transform the course ...
(Date:7/14/2017)... 13, 2017 It should come as no surprise ... is in the midst of a crippling opioid epidemic. According ... the number of overdose deaths from opiate-based medications has quadrupled, ... a million dead from 2001 to 2015". During this time, ... has similarly quadrupled, drawing a compelling link between prescription and ...
(Date:7/13/2017)... -- RK Logistics Group, Inc. was awarded California ... Fremont, CA headquarters facility where it provides ... San Jose for hi-tech, pharmaceutical and biomedical ... with its Fremont Innovation District, is excited to strategically partner ... to the hundreds of biotech, pharma and biomed companies throughout ...
Breaking Medicine Technology: