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Milos Spasic, PhD

Pronouns

He/Him/His

Job Title

Postdoctoral Researcher

Academic Rank

Research Fellow

Department

Medicine

Authors

Milos Spasic, Esther Ogayo, Adrienne Parsons, Tari King, Peter van Galen, Elizabeth Mittendorf, Sandra McAllister

Principal Investigator

Sandra McAllister

Research Category: Cancer

Tags

Deep immunoprofiling of peripheral blood by full-spectrum flow cytometry to characterize age- and race-associated changes in immune fitness

Scientific Abstract

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.

Lay Abstract

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.

Clinical Implications

Our work will lead to a blood test that indicates the risk of breast cancer and the development of age- and race-stratified treatments for breast cancer patients, as well as a myriad of other conditions impacted by immune function.