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

Abstract

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.