Breaking Through a Tumor’s Defense Mechanisms Could Improve Immunotherapy Results for Mesothelioma Patients

Recent breakthroughs in treating mesothelioma patients with immunotherapy drugs have brought the novel treatment into the spotlight. Still, only a small percentage of patients respond leaving researchers scrambling to understand why. Researchers now believe it is a tumor’s defense mechanism that evades immunotherapy, pointing to a new concept for developing improved immunotherapy drugs.

Immunotherapy works by boosting the patient’s own immune system to fight and destroy cancer cells.  But researchers from Babraham Institute in Cambridge, UK, report that tumors have two levels of protection that allows the cancers to thrive despite the attacks from the immune system, according to a June 6 press release. The researchers found that when one layer is knocked down the second layer takes over fighting off the immune system in earnest, defeating the immunotherapy.

https://babraham.ac.uk/news/2018/06/breaking-through-a-tumours-defences

The researchers determined that tumors, in effect, “recruit immune cell allies,” tumor-associated macrophages (TAMs) and regulatory T cells (Treg), to evade an attack from the immune system. They believe that in order to defeat this double protection layer of the tumors, a double layer of treatment is required.

“The research demonstrates that a two-pronged approach targeting both cell types simultaneously may offer a promising route for the development of new cancer immunotherapies,” reported the researchers.

Immunotherapy, although still in its early stages of use, has shown to be effective in some lung cancer patients. Keytruda and Opdivo, both FDA-approved for lung cancer, have extended the lives of some mesothelioma patients as well. Mesothelioma, an asbestos-caused cancer of the lining of the lungs, often follows the same mesothelioma cancer treatment protocol as non-small cell lung cancer. Not all patients are responsive to immunotherapy, which is why scientists continue their research into improving the effectiveness of what is considered a promising treatment.

Read about mesothelioma warrior Mavis Nye  achieving remission with Keytruda.

Using a mouse model of colorectal cancer, the researchers found a way to inhibit the recruitment of TAMs by blocking the colony-stimulating factor 1 (CSF1) protein, and found that tumor growth slowed. When they combined that by blocking Treg cells, the result “substantially inhibited tumour growth.”

“Harnessing the power of the immune system to kill cancer cells is becoming a successful therapeutic strategy. These studies demonstrate the importance of fully understanding the interplay between the many elements of the immune system to ensure that combinatorial therapies are both synergistic and effective,” said Professor Klaus Okkenhaug, one of the authors on the study.

The researchers concluded “These findings … provide a rationale for a new form of combinatorial immunotherapy.”

Nearly 3,000 Americans are diagnosed with mesothelioma each year, with approximately the same number dying from the incurable cancer. Immunotherapy has become the most promising treatment to increase survival in patients suffering from this aggressive cancer.

Read the full study in the June 7 issue of the journal JCI Insight.

https://insight.jci.org/articles/view/120631