Researchers are looking for other ways to disrupt tumor cells in a way that better engages the immune system by exposing it to tumor antigens.
Some cancers are more likely to be responsive to immunotherapy, but for different reasons. Endometrial cancer is now getting its time in the sun as several trials have matured to the point of showing clear benefits in patients with advanced cases already treated with chemotherapy
In this issue of CURE, you will learn why endometrial cancer may have unique sensitivity to immunotherapy and how this is transforming the treatment landscape. Genetic mutations are much more prevalent in tumor tissue compared with normal tissue as DNA repair abnormalities coupled with high cell division rates are seen in malignant cells. This results in abnormal proteins that are seen as “foreign” to the immune system and immune activation (known as making the tumor “hot”). This makes immunotherapy drugs like the check- point inhibitor Keytruda (pembrolizumab) more effective, as the immune system has already been “primed.
Because endometrial cancers can exhibit mismatch repair (MMR) deficiency, a type of DNA repair abnormality, this may explain why these cancers have been shown to respond to immunotherapy. Interestingly, the trials showed that even tumors that did not exhibit MMR defects benefit from the addition of immunotherapy. Such strategies are being moved in the first-line setting.
Researchers are looking for other ways to disrupt tumor cells in a way that better engages the immune system by exposing it to tumor antigens. This includes radiation and antiangiogenic drugs, both of which affect the tumor microenvironment in a pro-immunogenic direction. It is hoped that chemotherapy may even be omitted; this is being tested in ongoing clinical trials of immunotherapy with other biological drugs. The developments in endometrial cancer highlight the importance of understanding the details and nuances of how tumor cells interact with the immune “microenvironment” that surrounds and infiltrates tumors to variable extents.
Every day we learn more from basic science experiments and clinical trials for specific tumors that inform the next steps to being able to improve
DEBU TRIPATHY, M.D.
Professor of Medicine
Chair, Department of Breast Medical Oncology The University of Texas MD Anderson
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