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Altered gene linked to better outcomes of lymphoma treatment

Early lab testing shows promise for future immunotherapy trials
Dr. Christian Steidl and Dr. Shannon Healy, BC Cancer
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​Often stories of research breakthroughs highlight discoveries of abnormalities being a bad thing when trying to treat cancer. However, a recent BC Cancer discovery published February 24 in Nature Medicine by BC Cancer scientists Drs. Healy, Scott and Steidl in partnership with cancer researchers across the globe have uncovered the opposite is true for diffuse large B-cell lymphoma patients with a specific gene mutation in their tumours. Diffuse large B-cell lymphoma (DLBCL) is the most common form of blood cancer. 

The TMEM30A protein is present in every DLBCL cell, however cells with an altered gene were found to respond better to treatment when tested in the lab. The reason for this is two-fold and represents a significant step forward to better understanding cell biology. Firstly, chemotherapy is more effectively absorbed through the cell membrane of DLBCL cells with the mutated gene which means more medicine  can get into the tumour cells. This new understanding of tumour cell weakness can be exploited when treating patients. Secondly, cells with TMEM30A mutations are more easily identified by the body’s own immune system, in particular by cells called macrophages that have the ability to “eat” the tumour cells. 

“This discovery opens up new avenues investigating and understanding cell composition in cancer,” says Dr. Steidl, researcher at BC Cancer and senior author of the study. “It is one of only a few studies linking gene mutations to changes that we can therapeutically exploit.” 
“Recently, new medications have been discovered that enhance the ability of these macrophages to eat tumour cells. This discovery may identify patients that are particularly responsive to these new medicines” says Dr. Scott, clinician-scientist at BC Cancer and co-senior author. The hope is that this understanding can be applied more broadly to all cancers, beyond DLBCL. 

“Cancer has figured out a way to be more dangerous,” adds Dr. Healy, BC Cancer researcher and lead author of the study. “Now that we have learned about their vulnerabilities we can combat cancer more effectively.”
The next step will be to find novel drugs that can target the TMEM30A protein. This might make cancer cells more susceptible to treatment, including immunotherapies, and improve outcomes in the future.  
BC Cancer
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