Peter P. Lee
Response to cytokine signaling, as measured by a new blood test, may be an important determinant of intratumoral immunosuppressive potential and clinical outcome in patients with newly diagnosed breast cancer, according to study results published in Nature Immunology.
“This is the first success linking a solid tumor to blood biomarkers – an indicator of whether a patient will remain in remission,” Peter P. Lee, MD, chair of the City of Hope’s immuno-oncology division, in a press release. “When patients are first diagnosed with cancer, it is important to identify those at higher risk of relapse for more aggressive treatments and monitoring. Staging and new tests based on genomic analysis of the tumor are currently available for risk stratification. blood test would be even more attractive, but is not yet available, we are trying to change the status quo.”
Researchers collected data on 40 breast cancer patients followed over a median of 4 years. They validated the results in a separate cohort of 38 breast cancer patients.
The results showed that the blood of certain patients changed signaling to two pro- and two anti-inflammatory cytokines in regulatory T cells. The researchers used this data to create a cytokine signaling index that could process data through an algorithm that outputs a number to indicate the future risk of disease recurrence.
HemOnc Today spoke to Lee about the need for a test like this, how he and colleagues conducted the study, what they found, and what needs to be confirmed in future research.
Ask: NSy is a new test needed for this patient population?
Answer: After patients newly diagnosed with cancer undergo surgery with or without additional treatment, such as radiation or chemotherapy, they enter a period of waiting with great fear and anxiety that their cancer will come back. There has always been significant interest in a test that could stratify patients at diagnosis. There are some tumor tests available, such as the diagnostic test Oncotype DX (Genomic Health), which estimates the likelihood of disease recurrence in patients with early-stage breast cancer. Based on the recurrence score, doctors can select patients to be monitored more carefully or treated more aggressively. There has been no effective blood test like this.
Q: How did you conduct the research?
A: My group was interested in studying the immune system of patients with breast cancer for a long time. For the past 10 years we have looked at its function. Immune cells are like soldiers in an army; they have to communicate constantly. Most communication is through secreted molecules, also called cytokines, and many people measure these cytokines. We went one step further and measured both the cytokines and the recipient cell’s ability to respond to the cytokine.
Q: What have you found ?
A: We found that the signaling pattern in breast cancer patients is different from healthy controls, but we even found differences within patients. Patients who relapsed had abnormal signaling patterns, while those who did not relapse had a relatively normal preserved signaling pattern compared to healthy controls. Based on this knowledge, we applied the same test and thresholds to a validation cohort of breast cancer patients to see if our findings held up, and they did. In addition, the validation cohort predicted the results perfectly and confirmed our findings.
Q: What’s next for research?
A: While our results are exciting, in order to make them applicable to patients in the clinic in the future, we need to conduct a prospective study that includes more patients and follows them over several years. This would be a much larger study and would take more time and more money, which I hope we can get support for.
Q: Is there anything else you would like to mention?
A: Many research groups have measured cytokines, but what makes our research unique is that we measured the ability of immune cells to respond to cytokines. Some may wonder how this blood test compares to circulating tumor DNA. We’re measuring the host’s immune response, so we’re looking at the other side of the equation. We focus on the ability of the host’s immune system to prevent cancer cells from coming back. Because our test and circulating tumor DNA look at two different sides of the equation, these two tests could potentially be combined for an even more specific prediction. – by Jennifer Southall
For more information:
Peter P. Lee, MD , can be reached at City of Hope Comprehensive Cancer Center, 1500 Duarte Road, Duarte, CA 91010; email: firstname.lastname@example.org.
disclosure: Lee does not report any relevant financial disclosures.
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