Researchers Reveal How Tumors Manipulate Certain Immune Cells to Their Own Advantage

By Jennifer Bell, PhD, on
Pictured: Activated macrophage This scanning electron microscopy image shows an infection-fighting cell called a macrophage. Some macrophages that are located in tumors appear to help cancers grow. (Credit: Steve Gscheissner/Science Photo Library)
Summary

Researchers are exploring a mysterious population of immune cells that live within tumors and can help the cancer grow and spread.

Memorial Sloan Kettering researchers have uncovered the origins of a mysterious population of immune cells living within tumors and discovered how the tumors manipulate these cells to their own advantage.

The possibility of harnessing a patient’s own immune system to attack tumors was first proposed more than 100 years ago but has only very recently become a reality. Striking clinical trial results have shown that drugs that unleash the immune system’s T cells can successfully treat several different types of cancer, including late-stage metastatic melanoma. This and other successes prompted Science magazine to name cancer immunotherapy the top Breakthrough of the Year in 2013.

Now the push is on to discover novel immunotherapies that are even more effective. But the relationship between tumors and the immune system is complicated. Many different types of immune cells are found within tumors. For example, some types of T cells have the potential to attack tumors, while other immune cell populations seem to help cancers grow. Immunologist Ming Li at Memorial Sloan Kettering is investigating how the immune system responds to tumors and how the different immune cells that colonize solid tumors interact to influence cancer’s growth and spread.

Subverted Defense

In a new study published in Science, Dr. Li’s team zeroed in on immune cells called macrophages that are found scattered throughout solid tumors. In healthy tissues, macrophages are an essential first-line defense against infection, but tumor-associated macrophages (TAMs) appear to help cancers grow.

“Although several clinical studies show that patients with higher numbers of tumor-associated macrophages have a poorer prognosis, we do not know where these cells come from, what exactly they might be doing to promote tumor progression, or how to stop them,” explains Dr. Li.

Using a mouse model of breast cancer, his team explored the origins and molecular makeup of TAMs. They discovered that TAMs develop from white blood cells that migrate into tumors as they begin to grow and then proliferate there. The development of TAMs depended on the activation of a molecular signaling pathway called Notch.

When the researchers knocked out a critical gene in this signaling pathway, the development of TAMs was inhibited, while the number of T cells within the tumors capable of killing cancer cells increased and tumor growth was suppressed. They propose that TAMs may aid tumor growth by turning off cancer-killing T cells that enter the tumor.

“Based on what we know about conventional macrophages, we were surprised to find that TAMs divide and rely on Notch,” says first author and graduate student Ruth Franklin. “Our findings indicate that TAMs are very different to the nondividing macrophages that populate healthy breast tissue and suggest ways to specifically target these cells for tumor immunotherapy.”

The team is now testing whether these findings hold true for human TAMs. If so, immunotherapies that inhibit TAMs could be a powerful approach to unleash tumor-attacking T cells, particularly if used in combination with other T cell-directed immunotherapies.

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Benefits Beyond Cancer

Because the molecular fingerprint of TAMs is so different from that of macrophages that live in healthy tissues, Dr. Li suspects these cells represent a new type of immune response that may be important in other diseases.

Although macrophages that suppress T cells are bad news in cancer, in some situations they could be beneficial. For example, during chronic infections, excessive T cell activity can cause collateral damage to the body’s healthy tissues. Recruitment and proliferation of T cell–suppressing macrophages within tissues may have evolved as a way of protecting tissues from the immune system.

As tumors grow, they may in turn evolve ways to recruit and co-opt these specialized macrophages in order to ward off tumor-attacking T cells. To test this theory, the group is now exploring whether TAM-like cells arise during infections and in other disease settings.

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Comments

I have prostate cancer for 3rd time after 2 bouts radiation cancer confined to prostate am I a candidate for targeted immunotherapy or another clinical trialy

Philip, thank you for reaching out.

Here is a link to a listing of MSK clinical trials for prostate cancer, some of which involve immunotherapy:

http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=pr…All&phase=All

The trial descriptions list contact information is you would like to find out whether you may be eligible for a particular study.

If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment.

My friend has ovarian cancer for the past one and a half years. The first two medications have not been successful. Two new medications have now been introduced. The side effects are intense. She would like to know if she may be a candidate for your immunology program. We live in Las Vegas, Nevada. Please also advise if your immunology program is available in Nevada or California. Thank you for your consideration.

Dear David, thanks so much for your question. Here is an immunotherapy clinical trial that your friend may be eligible for: http://www.mskcc.org/cancer-care/trial/13-198. For other clinical trials we offer testing new therapies to treat ovarian cancer, please see this list: http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=&f…Ovarian+Cancer&phase=All. Just so you know, MSK is based in New York, and the immunotherapy trial is being offered in New York City specifically. For trials closer to home, you can search http://www.cancer.gov/clinicaltrials. Thanks so much for reaching out to us, and please let us know if you need anything else.

My husband had melanoma cut out of the white of his eye in June 2010. Three weeks ago he had surgery to place tube in tear duct so his eye would stop tearing
Surgeon ended up sending tissue from tear duct to pathology. It's melanoma. He has had pet scan, MRI and ct scan. A spot radiated a green spot on sternum. We are awaiting date/time for biopsy. I think it has metastasized . I'm reading about immunotherapy PD-1, Keytruda (pembrolizumab) -how do we get access to thisFDA approved drug for advanced stage melanoma? Please help

Connie, if your husband has not already done so, we recommend he meet with a medical oncologist, who will be able to tell him which drugs are most appropriate for his particular cancer. If you'd like to make an appointment to speak with someone at MSK, you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.

My friend is diagnosed with lung cancer - squamous cell. Is the immunotherapy available for this type of cancer and if so How can she apply.

SHE HAS ADVANCED STATEG 4 META PANCREATIC CANCER , IS A 4 1/2 YEAR SURVVIOR. WHAT CAN YOU OFFER ? DYING 4 HER FOR IS NOT AN OPTION.
EVEN IF SHE CANT GO INTO A CLININCAL TRIAL , WHY CANT CERTAIN DRUGS BE MADE AVAILABLE ALLOW HER THE OPPPORTUNITY TO POSSIBLY SURVIVE LONGER ? IM DISCUSTED THAT JUST BECAUSE SHE MAY NOT FIT INTO A TRIAL IT JUST MIGHT HELP HER BUT DOCTORS WILL LET HER DIE .

Thank you for reaching out, and we are sorry to hear of her diagnosis. If you are interested in possible treatments for pancreatic cancer --including clinical trials -- and would like a consultation with a Memorial Sloan Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment.

I had strange symptoms beginning in 2009 (right cheek lesion "rosacea like), swelling of my right ankle, my right index finger, dry eye, neck lymph node swelling) that various rhematologists/dermatologists tried to call SLE, sjogrens, before settlling on sarcoidosis after chest CT. No lung symptoms. July 2012 I developed a peristent low grade fever of unknown origin that lasted until October 2012. March 2013, I discovered a breast lump that was diagnosed as TNBC. FoundationOne study showed IKBKE mutation. I can't help but think all of this is related to immune system dysfunction. I developed liver mets immediately following chemo. Suggestions? Trials? Please help if you can.

Connie, thank you for reaching out. We are sorry to hear about your diagnosis. While we are unable to answer specific medical questions on our blog, if you would like a consultation with a Memorial Sloan Kettering physician regarding your breast cancer and the other symptoms you experienced, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thanks for your comment.

I have a very recent CT Chest with contrast 71260
suggesting various irregular somewhat spiculated mass in the interior lingule perpherally measuring 1.9 x 1.7 by 2.2 cm ...

can I fax the report to an oncologist for a follow up recommendation ?

Dear Robyn, please call our Physician Referral Service to discuss this further. The staff there can answer help answer your questions. Their number is 800 525 2225. Thanks for reaching out to us.

I just want to let you all know that the information about tumors and cancer in this section has been very informative. I also read about a wonderful mushroom named Ganoderma Lucidum that has properties, which inhibit tumor cells from grouping. Do you have further information about it and how effective is it?

would like to know more about Paget breast disease - was just diagnosed - had only a very little dryness on nipple which is gone. I am scheduled to have surgery thanks for any knowledge

my son inlaw: diagnosed stage 4B colan cancer on sept 2014...been thru folfoxiri & irinotecan plus pantitumamab: CT scan 6-12-15 shows tumors speading in liver and lungs: largest in lungs is 11mm, in liver 9cm shrunk to 5cm, but others growing. Otherwise good health. can you suggest a clinical trial? This candidate could show amazing results to you trial. thankyou

Susan, if your son-in-law would like to find out about clinical trials available at MSK, he can call our Physician Referral Service at 800-525-2225 during regular business hours to discuss clinical trials or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment.

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