A special blood test may one day predict if a newly diagnosed breast cancer patient will likely relapse years later, a study suggests.
“This is the first success linking a solid tumor with blood biomarkers – an indicator of whether a patient will remain in remission,” said the corresponding author of the study. “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.”
The effectiveness of a person’s anti-tumor immune response is determined by the balance between pro-inflammatory and anti-inflammatory signaling pathways in response to cytokines, according to the Nature Immunology study. The researchers used data on 40 breast cancer patients who were followed for a median of four years. Results were validated in a separate cohort of 38 additional breast cancer patients to create a benchmark that predicts if a breast cancer patient will likely relapse within a handful of years.
The balance of cytokine signaling responses in “peripheral blood immune cells” – the engine behind a healthy immune system – are indicators of the overall state of a person’s immune system, said the senior author.
“So, these findings may go beyond cancer to address other diseases the immune system must battle,” the senior author added. “This general approach may also be useful for predicting outcomes in patients with autoimmune and infectious diseases.”
A cancer patient’s peripheral blood immune cells, a critical part of the immune system, tends 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.
The authors analyzed signaling responses to many pro- and anti-inflammatory cytokines in different immune cell types that are found in peripheral blood from breast cancer patients 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 reflects the state of the immune system and predicts future relapse three to five years later.
Authors show that peripheral blood CD45RA−FOXP3hi Treg cells (Treg II cells) are phenotypically closest to intratumoral Treg cells, including in their expression of CCR8. Analyses of T cell antigen receptor repertoires further supported the hypothesis that intratumoral Treg cells may originate primarily from peripheral blood Treg II cells. Moreover, the signaling responsiveness of peripheral blood Treg II cells to immunosuppressive, T helper type 1 (TH1) and T helper type 2 (TH2) cytokines reflects intratumoral immunosuppressive potential, and predicts future relapse in two independent cohorts of patients with breast cancer.
The scientists used their data to create a cytokine signaling index (CSI), a sort of benchmark. The idea is that a patient could go in for a blood test and have their data run through an algorithm that will output a number which informs doctors what the patient’s risk of cancer recurrence is within three to five years.
“Knowing the chance of cancer relapse will inform doctors how aggressive a particular patient’s cancer treatment should be,” the senior author 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.”
Blood test may predict risk of recurrence for breast cancer patients
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