Featured Research

from universities, journals, and other organizations

Rare Immune Cell Is Key To Transplant's Cancer-killing Effect

Date:
October 17, 2005
Source:
University of Michigan Health System
Summary:
University of Michigan researchers have discovered the secret weapon behind the most powerful form of cancer immunotherapy known to medicine. Scientists call it the graft-versus-leukemia effect, and it occurs when new immune cells from donated bone marrow, called the graft, attack malignant cells in the patient and destroy them. This intense immune reaction between donor and host cells, which follows a bone marrow transplant from a healthy donor, has saved the lives of thousands of patients with leukemia, lymphoma and other types of blood and immune system cancers.

An antigen presenting cell interacting with two T cells.
Credit: Pavan Reddy, U-M Medical School

ANN ARBOR, Mich. -- Researchers at the University of Michigan'sComprehensive Cancer Center have discovered the secret weapon behindthe most powerful form of cancer immunotherapy known to medicine.

Related Articles


Scientists call it the graft-versus-leukemia effect, and it occurs whennew immune cells from donated bone marrow, called the graft, attackmalignant cells in the patient and destroy them. This intense immunereaction between donor and host cells, which follows a bone marrowtransplant from a healthy donor, has saved the lives of thousands ofpatients with leukemia, lymphoma and other types of blood and immunesystem cancers.

In a study to be published Oct. 16 in the advanced onlineedition of Nature Medicine, U-M scientists describe how antigenpresenting cells are crucial to graft-versus-leukemia's cancer-killingeffect.

The discovery is significant, because it could help make cellularimmunotherapy safer, more effective and an option for more cancerpatients -- especially those for whom a donor is unavailable or thosewho cannot tolerate the procedure's side-effects.

"We already knew that donor T cells were important for aneffective GVL response, but now we know there's another cell -- theantigen presenting cell or APC -- which plays a critical role in theprocess," says James L.M. Ferrara, M.D., who directs the U-M CancerCenter's Blood and Marrow Transplant Program.

Antigen presenting cells are rare immune system cells, which looksomething like a starfish. Their job is to digest proteins calledantigens from foreign cells or pathogens and present them to T cells.This alerts the immune system to prepare to fight the invader. WhenAPCs present cancer cell proteins to T cells, the T cells are primed toattack the cancer.

"We found that without functional APCs to process and presentantigens to T cells, there is no graft-versus-leukemia response, andthe cancer is likely to return," says Pavan R. Reddy, M.D., anassistant professor of internal medicine in the University of MichiganMedical School, who led the research study.

According to Reddy, the research results suggest that manipulating thenumber and activity of APCs could improve the GVL response, whilereducing the risk of a common post-transplant complication calledgraft-versus-host disease, or GVHD.

"GVHD occurs when the donor's immune cells attack thepatient's skin, liver and gastrointestinal tract," Reddy explains. "Ittriggers a massive inflammatory reaction that can kill the patient,especially if he or she is older or has other medical problems."

In an effort to eliminate GVHD, other researchers havesuggested removing APCs from transplanted donor cells, according toFerrara. "We know that APCs are involved in graft-versus-host disease,so people say let's take out the APCs and then we will get theanti-cancer effect without the risk of GVHD," he explains. "This papersays, no, you can't do that.

"There's a tight link between the graft-versus-leukemia effectand graft-versus-host disease," Ferrara says. "Few patients get thebeneficial effects of GVL without some degree of the toxic side effectsof GVHD. But if we can find ways to reduce GVHD's toxic effects,immunotherapy could become a viable option for many more cancerpatients."

To study what happens during the graft-versus-leukemia effect,Reddy and his U-M colleagues used high doses of radiation to destroythe blood and immune systems of genetically different laboratory mice.After reconstituting each animal's immune system, using eitherfunctional or non-functional APCs, the mice were inoculated with cancercells and given a bone marrow transplant that could cure the cancer.The scientists then determined which mice died from acutegraft-versus-host disease, which mice died from cancer and which micegenerated a GVL response to destroy the cancer cells.

"The donor and host mice were paired in ways to make theirantigen-presenting cells dysfunctional, either because they were of thesame tissue type as the donor, or because they had a mutation thatprevented them from displaying tumor antigens to T cells," Reddyexplains. "Essentially we created animals where the tumor was the same,the antigens were the same, donor T cells were the same, but the APCwas dysfunctional. Without a functioning APC, there was nograft-versus-leukemia effect."

Other researchers have suggested that tumor cells can presentantigens to T cells directly to stimulate an immune response againstcancer, but results from the U-M study indicate the response is tooweak to be effective.

"APCs shred proteins, or antigens, from cancer cells anddisplay those shredded proteins on their surface," Ferrara says."Cancer cells have the same proteins, but haven't gone through theAPC's shredding process. It's as if APCs are master chefs who preparethe antigens in a way to make them especially delicious to T cells. Soinstead of taking just one bite, they go back for seconds or thirds."

In future research, U-M scientists will explore how tomanipulate APC function in ways that will preserve their vital role instimulating an immune response against cancer, while controlling theintensity of graft-versus-host disease. Reddy and Ferrara have studieddrugs called HDAC inhibitors and found that they modulate APC functionin mice. They hope to design an initial study of these drugs inpost-transplant leukemia patients within a year.

###

The research was funded by the National Cancer Institute.Collaborators included Yoshinobu Maeda, M.D., a former U-M researchfellow; Oleg I. Krijanovski, M.D., a research fellow in internalmedicine; Chen Liu, M.D., a pathologist at the University of FloridaCollege of Medicine; and Robert Korngold, M.D., Ph.D., an immunologistand scientific director of the Hackensack University Cancer Center.


Story Source:

The above story is based on materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.


Cite This Page:

University of Michigan Health System. "Rare Immune Cell Is Key To Transplant's Cancer-killing Effect." ScienceDaily. ScienceDaily, 17 October 2005. <www.sciencedaily.com/releases/2005/10/051017072731.htm>.
University of Michigan Health System. (2005, October 17). Rare Immune Cell Is Key To Transplant's Cancer-killing Effect. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2005/10/051017072731.htm
University of Michigan Health System. "Rare Immune Cell Is Key To Transplant's Cancer-killing Effect." ScienceDaily. www.sciencedaily.com/releases/2005/10/051017072731.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins