Summary: Team paves the way for cancer immunotherapy with a novel technique that attacked tumors and inhibited cancers from spreading. [This article first appeared on LongevityFacts. Author: Brady Hartman. ]
While cancer immunotherapy is a powerful treatment for some types of tumors, up until now, it hasn’t worked well on colon cancer
However, a team of researchers in Barcelona just showed a new technique that allows the immune system to recognize and begin fighting the tumor in mice. The treatment was so successful that it inhibited the tumors from spreading, or metastasizing to other parts of the body – as cancer is prone to do. Moreover, for those cancers that had already spread, the treatment enabled the immune system to eliminate them quickly.
While immunotherapy works well in treating lung cancer and melanoma, most colon cancers have been unresponsive to the novel treatment, leading researchers to believe that colon tumors are invisible to the immune system. In a study published February 14 in the journal Nature, a team led by Eduard Batlle, at the Institute for Research in Biomedicine (IRB) in Barcelona, discovered that the hormone TGF-beta is to blame for the colon cancer cells being invisible to the immune system. The IRB team is convinced that many colon cancer patients will benefit and says that pharmaceutical firms will shortly start developing clinical assays that implement this therapeutic strategy.
Enabling Immunotherapy for Colon Cancer
For want of a more effective treatment, about 40 to 50% of colon cancer patients relapse, their tumors metastasizing and spreading to the liver and lungs. As Eduard Batlle says,
“Once advanced stage colon cancer is diagnosed, oncologists do not have access to efficient treatments to cure the patient.”
This new study paves the way for the first immunotherapy treatment of metastatic colon cancer as well as for patients with a poor prognosis who have not yet developed metastasis.
TGF-beta inhibitors are already in clinical use, and Batlle’s team observed that inhibiting the activity of TGF-beta, allowed the immune system to recognize and infiltrate and begin fighting the tumor. The treatment even inhibited colon tumors from metastasizing to the lung and liver in mice specially bred to mimic human cancer. More importantly, the scientists demonstrated that combining a TGF-beta inhibitor with cancer immunotherapy boosted the anti-tumor effect, allowing the immune system to quickly eliminate established metastases. These metastases would have otherwise killed the patient in a few weeks.
How They Did It
Daniele Tauriello is a postdoctoral fellow and as the first author of the article. Dr. Tauriello was instrumental in developing the mice models used by the research team. The models mimic the main features of metastatic colon cancer in humans, allowing the scientists to examine how cancer cells manage to evade the immune system. As Tauriello says,
“The development of the animal model took us four years, but we hit the nail on the head.”
After confirming the similarity of the mouse cancers with those in humans, the team built a biobank of mini-tumors called tumor organoids and grafted them into immunocompetent mice. As Tauriello explains,
“For studies of the immune system, the tumour has to be of mouse origin. Otherwise, the animal would reject it,”
The odds of getting cancer increases with every birthday. About half of those living in industrialized nations will develop cancer during their lifetimes, usually after the age of 40. Cancer kills slightly under 8 million people worldwide every year. Most cancers are caused by DNA damage, genetics, weakened immune systems, or environmental exposure to carcinogens such as cigarette smoke, pollution or other toxins.
Until recently, medical advances in tumor treatment have not kept pace with the striking decline in cardiovascular deaths that have occurred since 1950. The mainstays of tumor treatment have long been radiation therapy, surgery, and chemotherapy. While these treatments save lives, most physicians have shifted their focus to advanced tumor treatments such as immunotherapy.
One reason that tumors thrive is that they can hide from the immune system. Cancer cells adapt to live in a highly inflamed environment, evade recognition by the immune system and suppress the immune response.
Cancer immunotherapy overcomes these tumor survival strategies and strengthens the immune system fight cancer. Researchers have long noted that young people with a robust immune system rarely get cancer. A healthy immune system seeks out and destroys many cancerous or precancerous cells.
Immunotherapy for Colon Cancer and More
The IRB team is convinced that many colon cancer patients will benefit from this therapeutic strategy and says that pharmaceutical firms will shortly start developing clinical assays that combine TGF-beta inhibitors with immunotherapies.
Another study in the same issue of the journal Nature reached similar conclusions. This study, conducted by the U.S. pharmaceutical company Genentech, addressed the lack of response to immunotherapy witnessed by bladder cancer patients. Commenting on the Genetech study, Batlle says
“This second study demonstrates that the discovery goes beyond colon cancer. It appears that many types of tumour use the same strategy—increasing the expression of TGF-beta in the environment—to evade the immune system. Patients with these tumours may also benefit from immunotherapies based on the inhibition of this hormone.”
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Cover Photo: Getty Images.
“Team paves the way to the use of immunotherapy to treat aggressive colon tumors.” Institute for Research in Biomedicine (IRB Barcelona). February 15, 2018. Link to the press release in MedicalXpress.
More information: Daniele V. F. Tauriello et al., “TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis.” Nature. February 14, 2018. DOI: 10.1038/nature25492. Link to the article in Nature.
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