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Longitudinal Modulation of Loco-Regional Immunity in Ovarian Cancer Patients Receiving Intraperitoneal Chemotherapy
Adria Suarez Mora1,2,3, Mary Strange2, Yusi Fang4
1Department of Obstetrics and Gynecology and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Chemotherapy for epithelial ovarian cancer (EOC) alters the immune tumor microenvironment (TME), boosting B cell function and Th2 immunity while dampening Th1 responses. Serial sampling effectively tracks these dynamic immune changes.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- The immune tumor microenvironment (TME) in epithelial ovarian cancer (EOC) exhibits complex effector and suppressive roles.
- Understanding immune changes during chemotherapy is crucial for predicting treatment response and tumor involution.
Purpose of the Study:
- To longitudinally evaluate biomarker expression in serial specimens during intraperitoneal (IP) platinum-based chemotherapy for EOC.
- To identify immune correlates of chemotherapy-induced tumor involution.
Main Methods:
- Longitudinal collection of serial biological samples (IP fluid, plasma, tumor tissue) during IP chemotherapy.
- Analysis of RNA via NanoString, Meso Scale Discovery (MSD) multiplex assay, and ELISA for anti-MUC1 antibodies.
- Evaluation of gene expression and protein markers to assess immune cell function and activation.
Main Results:
- Chemotherapy induced an upregulation of B cell function and Th2 immune responses, alongside a dampening of Th1 immunity in IP fluid.
- MSD and gene expression analyses confirmed Th2 immunity activation and complement system involvement.
- Anti-MUC1 antibodies were detected in IP fluid, and IP fluid analysis revealed chemotherapy-induced B cell function genes in a secondary cohort.
Conclusions:
- Serial intraperitoneal fluid sampling is an effective method for capturing dynamic changes in the EOC immune TME during chemotherapy.
- The study reveals chemotherapy-induced alterations in B cell function and Th2-biased immunity.
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