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Role of Regulatory T Cells in Predicting Breast Cancer Relapse

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Key Points

  • Researchers found altered signaling to four different cytokines (two pro- and two anti-inflammatory) in regulatory T cells in some patients.
  • These cytokine signaling patterns in peripheral blood at diagnosis reflect the state of the immune system, and may predict future relapse 3 to 5 years postdiagnosis.

Blood and intratumoral regulatory T-cell activity may one day provide a method for predicting breast cancer relapse, according to findings published by Wang et al in Nature Immunology.

“This is the first success linking a solid tumor with blood biomarkers—an indicator of whether a patient will remain in remission,” said corresponding study author Peter P. Lee, MD, chair of the Department of Immuno-Oncology at City of Hope. “When patients are first diagnosed with cancer, it is important to identify those at higher risk for relapse for more aggressive treatments and monitoring. Staging and new tests based on genomics analysis of the tumor are currently available for risk stratification. However, a predictive blood test would be even more attractive but is not yet available. We are trying to change the status quo.”

Methods

The effectiveness of a patient’s antitumor immune response is determined by the balance between pro- and anti-inflammatory signaling pathways in response to cytokines, according to researchers. Dr. Lee and colleagues used data from 40 patients with breast cancer who were followed for a median of 4 years. Results were validated in a separate cohort of 38 additional patients to create a benchmark that predicts if a patient will likely relapse within several years.

The balance of cytokine signaling responses in peripheral blood immune cells are indicators of the overall state of a person’s immune system, said Dr. Lee.

“...These findings may go beyond cancer to address other diseases the immune system must battle,” he added. “This general approach may also be useful for predicting outcomes in patients with autoimmune and infectious diseases.”

A patient with cancer’s peripheral blood immune cells tend to have decreased pro-inflammatory cytokine signaling responses and increased immune suppressive cytokine signaling responses, meaning a systemic immune environment is created that is conducive to the spread of cancer.

Findings

Dr. Lee and his colleagues analyzed signaling responses to many pro- and anti-inflammatory cytokines in different immune cell types that are found in peripheral blood from patients with breast cancer who were newly diagnosed with the disease. They found altered signaling to four different cytokines (two pro- and two anti-inflammatory) in regulatory T cells in some patients. These cytokine signaling patterns in peripheral blood at diagnosis reflect the state of the immune system, and may predict future relapse 3 to 5 years postdiagnosis.

The scientists used their data to create a cytokine signaling index (CSI). “Knowing the chance of cancer relapse will inform doctors how aggressive a particular patient’s cancer treatment should be,” Dr. Lee said. “The CSI is an overall reflection of a patient’s immune system at diagnosis, which we now know is a major determinant of future relapse.”

The investigators concluded, “Together, our findings give important insights into the relationship between peripheral blood regulatory T cells and intratumoral regulatory T cells, and highlight cytokine signaling responsiveness as a key determinant of intratumoral immunosuppressive potential and clinical outcome.”

Disclosure: The study was supported by the U.S. Department of Defense Breast Cancer Research Program, Stand Up to Cancer, Breast Cancer Research Foundation, and the V Foundation. For full disclosures of the study authors, visit nature.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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