Milos Spasic, PhD
Milos Spasic, Esther Ogayo, Adrienne Parsons, Tari King, Peter van Galen, Elizabeth Mittendorf, Sandra McAllister
Research Category: Cancer
The immune system plays a critical role in dictating cancer progression and responses to therapy. Numerous factors, such as age and race, impact immune system function and understanding these changes will enable us to develop patient-specific cancer therapies. Here, we developed full-spectrum flow cytometry immunoprofiling panels for analysis of peripheral blood mononuclear cells at single cell resolution. We developed two panels to fully characterize T and B cell subsets, as well as monocytic, dendritic, and NK cells, along with functional and exhaustion markers. To study the impact of age and race on immune profiles, we analyzed samples from the Brigham and Women’s Hospital B-PREP (Breast Cancer Personalized Risk Assessment Education, and Prevention) program. Samples were stratified by younger (65) patients, as well as non-Hispanic Black (NHB) and non-Hispanic-White (NHW) patients with high risk lesions and non-high risk lesions. This will serve as a baseline as we continue to monitor patients through breast cancer progression. The analysis platform, OMIQ, was used to perform unbiased clustering in FlowSOM to identify unique populations of cells, while traditional gating was used to quantify proportions of canonical cell populations highlighting hallmarks of premature immunological aging in Black patients.
Age is the greatest risk factor for developing most forms of cancer. During aging, our immune system undergoes changes impacting the fitness of our immune system and ability to fight disease. Furthermore, non-Hispanic black (NHB) patients typically have worse outcomes across many forms of cancer compared to non-Hispanic white (NHW) patients. We hypothesize that NHB patients experience premature immunological aging for various reasons, including race-related stress, thus resulting in worse outcomes. To better understand patient-specific differences in immune system function, we developed a new analysis tool to profile immune cells in the blood. Our analysis tool will tell us whether critical immune cells from NHB women have properties similar to immune cells from older individuals. Our analysis platform will also help us understand how age- and race-associated changes in the immune system may impact the risk of developing breast cancer. Our initial analysis of blood samples from young and older NHW women and middle-aged NHB and NHW patients suggest that NHB women have similar traits as the samples from older women. Through this we have identified hallmarks of immune weathering and pre-mature aging in NHB patients.