Dr. Grivas on Mechanisms of Immune Response in Bladder Cancer

Petros Grivas, MD, PhD
Published: Monday, Dec 17, 2018



Petros Grivas, MD, PhD, director, University of Washington Medicine’s Genitourinary Cancers Program, associate professor, Oncology, University of Washington, Seattle Cancer Care Alliance, discusses mechanisms of immune response in bladder cancer.

Although there is not yet an established biomarker for immunotherapy response in this space, there is some understanding on the reason why patients with bladder cancer have benefitted from the rise of immune checkpoint inhibitors. For example, many of these patients have a high tumor mutational burden (TMB), which results in the creation of proteins called neoantigens, explains Grivas. Once recognized by the immune system, these neoantigens can qualitatively boost immunogenic response.

The challenge is locating the robust, activating neoantigens, a feat that Grivas compares to be as difficult as finding a needle in a haystack. However, statistically, a higher TMB has been associated with increased immune response to checkpoint inhibitors, across tumor types. He adds that early data indicate that patients with mutations in the DNA damage repair pathway may have higher response rates to immunotherapy. The unanswered question is whether this mechanism is due to genomic instability or if it is a separate mechanism of immune response entirely.

Molecular subtype profiling data need to be investigated further, Grivas adds, as some cancer subtypes may respond better to immune checkpoint inhibitors compared with others.
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Petros Grivas, MD, PhD, director, University of Washington Medicine’s Genitourinary Cancers Program, associate professor, Oncology, University of Washington, Seattle Cancer Care Alliance, discusses mechanisms of immune response in bladder cancer.

Although there is not yet an established biomarker for immunotherapy response in this space, there is some understanding on the reason why patients with bladder cancer have benefitted from the rise of immune checkpoint inhibitors. For example, many of these patients have a high tumor mutational burden (TMB), which results in the creation of proteins called neoantigens, explains Grivas. Once recognized by the immune system, these neoantigens can qualitatively boost immunogenic response.

The challenge is locating the robust, activating neoantigens, a feat that Grivas compares to be as difficult as finding a needle in a haystack. However, statistically, a higher TMB has been associated with increased immune response to checkpoint inhibitors, across tumor types. He adds that early data indicate that patients with mutations in the DNA damage repair pathway may have higher response rates to immunotherapy. The unanswered question is whether this mechanism is due to genomic instability or if it is a separate mechanism of immune response entirely.

Molecular subtype profiling data need to be investigated further, Grivas adds, as some cancer subtypes may respond better to immune checkpoint inhibitors compared with others.



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