Nav: Home

Cancer commandeers immature immune cells to aid its successful spread

April 06, 2017

AUGUSTA, Ga. (April 6, 2017) - More typically, these immature immune cells might help us fight cancer, but scientists have now shown cancer can commandeer the cells to help it spread.

Cancer uses myeloid-derived suppressive cells, or MDSCs, that come from the bone marrow, like a support system to successfully metastasize, report scientists at the Georgia Cancer Center at Augusta University.

While cancer early and often sends out cells from its primary site - like the lungs or breast - to other organs, most cells don't survive immune system surveillance. Still, 90 percent of cancer deaths are related to metastasis.

"These cells are essential to successful cancer metastasis," said Dr. Hasan Korkaya, molecular and cancer biologist at the Georgia Cancer Center and Medical College of Georgia at AU.

While it's known MDSCs, found in high levels in mouse models and patients with cancer, are good at suppressing the immune response, their role in enabling tumors to spread and succeed is emerging, said Korkaya, corresponding author of the study in the journal Nature Communications. Dr. Maria Ouzouonova, who just completed her postdoctoral fellowship in Augusta, and fourth-year graduate student Eunmi Lee are co-first authors on the study.

It's thought that the tumors cells about to leave the primary site become stem-cell like so they can free themselves from the primary tumor, and more easily migrate to and populate a new area. Once there, they revert to a state that enables them to take up residence.

The new study shows commandeered MDSCs aid both: One type - monocytic MDSCs - help tumor cells make the stem-cell like transformation while another- granulocytic MDSCs - helps them essentially revert, settle in and grow.

MDSCs appear to get their wayward direction from cytokines, in this case, secreted by the tumor. Cytokines are small signaling proteins normally secreted by the immune system to influence other cell types. But a tumor also can secrete these chemical messengers, and the message it sends to these immature myeloid cells is to support it.

"They are being schooled toward facilitating tumor cell growth and metastasis," Korkaya said. Like bad parents, tumors also use cytokines to keep the MDSCs from maturing so they can keep telling them what to do.

"There is a very intricate balance in the immune system that is usually anti-tumorigenic, meaning it eliminates tumors, but in some cases, if this balance is altered, these cells may actually help tumors grow and develop into full-blown metastatic disease," Korkaya said.

Even prior to the newly published study, Korkaya strongly suspected that a cocktail of certain cytokines would enable tumors to turn the suppressive power of MDSCs to their advantage. In his earlier mouse work at the University of Michigan, for example, Korkaya was among the first to show that when he used an antibody to eliminate cytokine IL-6, it significantly reduced metastasis of breast cancer in mice. Anti-IL-6 therapies are now in clinical trials.

He's not yet certain whether MDSCs travel with migrating tumor cells or if they are an advance team that readies their future remote location. But when he looks at tumor cells in his current mouse model of breast cancer, the ones that have taken hold in a new organ are surrounded by MDSCs.

Rather than eliminating the large volume of wayward cells, Korkaya and his research team are already exploring ways to re-school them to fight rather than support tumors. That includes finding ways to target cytokines found in high levels in metastatic disease.

Most of us without cancer have low levels of MDSCs and very few circulating in the blood, rather they tend to be undifferentiated cells waiting, mostly still in the bone marrow, for a call to action, like a bacterial infection or tumor.

MDSCs also are known to be a major impediment to successful immunotherapy, in which agents are used to strengthen the ability of the patient's immune system to battle cancer. In fact, recent studies have suggested that MDSCs may have to be eliminated for immunotherapy to be optimally successful, Korkaya said. The cells also appear to have a role in angiogenesis, or helping tumors form blood vessels they need to survive once they reach a certain size.

Some types of cytokines are actually used to treat cancer and/or to offset other negative effects of chemotherapy, like helping make more healthy red blood cells in response to the loss of these cells that occurs with treatment.
-end-


Medical College of Georgia at Augusta University

Related Breast Cancer Articles:

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.
Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.
Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.
Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
Blood test offers improved breast cancer detection tool to reduce use of breast biopsy
A Clinical Breast Cancer study demonstrates Videssa Breast can inform better next steps after abnormal mammogram results and potentially reduce biopsies up to 67 percent.
More Breast Cancer News and Breast Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.