Response to bladder cancer immunotherapy can be genetically predicted

Anti-PD-1/PD-L1 therapy, a type of cancer immunotherapy that opens the door for the body’s immune system to attack tumor cells, has proven effective against many types of cancer. mail in the past 5 years.

Keith Syson Chan, Ph.D., translation scientist, professor of Pathology and co-author of the study, said, “It has been shown to be very effective against melanoma and revolutionizes the treatment of cancer. Bladder cancer is considered one of the more responsive tumor types, but still only has a 25% long-term response rate, so improvement is still needed.”


When a tumor triggers a host immune response, it is called a ‘hot’ tumor because immune cells frequently enter the tumor’s interior. On the other hand, some cancers, known as ‘cool’ tumors, prevent immune cells from entering.

A gene called tyrosine kinase 2 (DDR2) of the discoidin domain receptor has been linked in a previous study by Theodorescu to resistance to PD-1 in animal models of several tumor types. This new study used human cancer datasets in different tumor types in a collaboration between cancer biologists and bioinformatics experts to better analyze the DDR gene family.

As the study’s first author, Sungyong You, Ph.D., a computer biologist with experience in urinary cancer, examined information from the Cancer Genome Mapping program, a facility freely accessible data with details on hundreds of cancer samples, to examine the relationship between expression of related genes DDR1 and host immune response to tumor using bladder cancer model making. He also studies the correlation between genes controlled by DDR2 and DDR1 (also known as gene symbols). He then examined patient data from IMvigor 210, a clinical trial evaluating the effectiveness of immunotherapy in the treatment of bladder cancer, to see if these results were related to expression. of DDR2 and DDR1 or their related gene profiles.

The investigators concluded

First, despite belonging to the same gene family, the DDR1 and DDR2 genes have extremely different effects on cancer. DDR2 expression is often low in tumors with high DDR1 expression, and vice versa. Furthermore, while high DDR2 volumes are ‘hot’, high DDR1 volumes are ””.

The researchers also discovered four distinct gene profiles that were strongly correlated with tumor response to immunotherapy and controlled by DDR1 and DDR2. These genetic markers have also been studied in other publicly available patient data collections from different cancer types.

“We found that these gene markers were clearly associated with response to immunotherapy in bladder and lung cancer in a wide range of patient populations,” You said.

“The next step is to validate these signatures in a potential clinical trial. This could yield new tools that allow clinicians to identify, before treatment, patients presented with response to anti-PD-1/PD-L1 therapy, they can then continue with anti-PD-1/PD-L1 therapy for those patients who will derive the most benefit and provide develop alternative therapies for patients who are unlikely to respond, improving outcomes for everyone,” said Theodorescu.

Source: Eurekalert

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