Effect of External Beam Radiation Therapy and Brachytherapy on Circulating Myeloid-Derived Suppressor Cell Populations in Patients Treated Definitively for Cervical Cancer

Kelsey M. Wanhainen, MD, PhD; Matthew Berkseth, PhD; Nicole Sando, BS; Lydia Golden, BS; Amy Techam, RN, PHN; Jennifer Wieworka, DNP; Kyra M. Boorsma Bergerud, BS; Peter Argenta, MD; Andrea O'Shea, MD; Britt K. Erickson, MD; Sally Mullany, MD; Colleen Rivard, MD; Rahel Ghebre, MD, MPH; Deanna Teoh, MD, MS; Margaret Reynolds, MD; Stephanie Terezakis, MD; Jianling Yuan, MD, PhD; Lindsey Sloan, MD, PhD

Advances in Radiation Oncology (Feb 2025)

Effect of External Beam Radiation Therapy and Brachytherapy on Circulating Myeloid-Derived Suppressor Cell Populations in Patients Treated Definitively for Cervical Cancer

Kelsey M. Wanhainen, MD, PhD,
Matthew Berkseth, PhD,
Nicole Sando, BS,
Lydia Golden, BS,
Amy Techam, RN, PHN,
Jennifer Wieworka, DNP,
Kyra M. Boorsma Bergerud, BS,
Peter Argenta, MD,
Andrea O'Shea, MD,
Britt K. Erickson, MD,
Sally Mullany, MD,
Colleen Rivard, MD,
Rahel Ghebre, MD, MPH,
Deanna Teoh, MD, MS,
Margaret Reynolds, MD,
Stephanie Terezakis, MD,
Jianling Yuan, MD, PhD,
Lindsey Sloan, MD, PhD

Affiliations

Kelsey M. Wanhainen, MD, PhD: University of Minnesota Medical School, Minneapolis, Minnesota
Matthew Berkseth, PhD: Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota
Nicole Sando, BS: Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota
Lydia Golden, BS: Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota
Amy Techam, RN, PHN: M Health Fairview, Minneapolis, Minnesota
Jennifer Wieworka, DNP: M Health Fairview, Minneapolis, Minnesota
Kyra M. Boorsma Bergerud, BS: Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota
Peter Argenta, MD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Andrea O'Shea, MD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota
Britt K. Erickson, MD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Sally Mullany, MD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota
Colleen Rivard, MD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Rahel Ghebre, MD, MPH: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Deanna Teoh, MD, MS: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Margaret Reynolds, MD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Stephanie Terezakis, MD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Jianling Yuan, MD, PhD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Lindsey Sloan, MD, PhD: University of Minnesota Medical School, Minneapolis, Minnesota; Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Corresponding author: Lindsey Sloan, MD, PhD

Journal volume & issue: Vol. 10, no. 2
p. 101677

Abstract

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Purpose: The immunosuppressive function of myeloid-derived suppressor cells (MDSCs) has been implicated in the regulation of immune responses against cancer and is associated with poor prognosis. Radiation treatment is known to alter immune cell populations within the tumor; however, whether this results in the recruitment of immunosuppressive MDSC populations is not well understood. Here we evaluate the response of circulating MDSC populations in patients treated per standard-of-care cisplatin chemoradiation therapy (CRT) for locally invasive cervical cancer. Methods and Materials: Newly diagnosed, treatment-naïve patients with locally advanced cervical cancer were enrolled. Blood samples were collected from patients prior to starting CRT (T0), after external beam radiation therapy (T1), and after high-dose-rate brachytherapy (T2). Samples from each time point were processed, and the prevalence of MDSC subsets was determined using flow cytometry. MDSC populations were identified using Live/Dead-CD11b+CD33+HLA-DR- staining. MDSC subsets were further subdivided into granulocytic (g-, CD15+CD14-), monocytic (m-, CD15-CD14+), or early-MDSCs (e-, CD15-CD14-). Results: Most patients in our study were Caucasian nonsmokers with human papillomavirus-associated squamous cell carcinoma of the cervix. We saw a trend for increased MDSC frequency in patients with more advanced-stage disease at the time of initiating treatment. MDSCs increase in response to CRT and peak after brachytherapy (T2). In particular, the g-MDSC subset increases by 6.44 times relative to the baseline. There was no correlation between MDSC expansion and response to therapy. Conclusion: Our study confirms other reports that circulating MDSCs in patients with cervical cancer increase in response to CRT and are associated with more advanced stages. Additionally, we show that MDSC expansion is driven by the g-MDSC subset. We did not see any correlation between MDSC expansion and treatment response, though this may be because of the limited sample size for this study.

Published in Advances in Radiation Oncology

ISSN: 2452-1094 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General): Medical physics. Medical radiology. Nuclear medicine; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/advances-in-radiation-oncology/

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