Circulating Neutrophils and Tumor-Associated Myeloid Cells Function as a Powerful Biomarker for Response to Chemoradiation in Locally Advanced Cervical Cancer

Authors

Olsi Gjyshi
Adam Grippin
Lauren Andring
Anuja Jhingran
Lilie L Lin
Julianna Bronk
Patricia J Eifel
Melissa M Joyner
Jagannadha K Sastry
Kyoko Yoshida-Court
Travis N Solley
Tatiana Cisneros Napravnik
Madison P O'Hara
Venkatesh L Hegde
Lauren E Colbert
Ann H Klopp

Publication Date

3-1-2023

Journal

Clinical Translational Radiation Oncology

Abstract

PURPOSE: The immune system's role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC).

MATERIAL AND METHODS: Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7 weeks, range 8.1-25.1 weeks for the prospective cohort and 5.3 weeks with a range of 2.7-9.0 weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry.

RESULTS: In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b

CONCLUSIONS: These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity.

Keywords

Neutrophils, Biomarker, Radiation oncology, Cervical cancer, Immunobiology

Comments

Supplementary Materials

PMID: 36935860