PARP inhibition is a modulator of anti-tumor immune response in BRCA-deficient tumors
Anna D. Staniszewska, Joshua Armenia, Matthew King, Chrysiis Michaloglou, Avinash Reddy, Maneesh Singh, Maryann San Martin, Laura B. Prickett, Zena Wilson, Theresa A. Proia, Deanna L. Russell, Morgan Thomas, Oona Delpuech, Mark J. O’Connor, Elisabetta Leo, Helen K. Angell, Viia Valge-Archer
Abstract
, olaparib induced BRCAm tumor cell-specific dendritic cell transactivation. Relevance to human disease was assessed using patient samples from the MEDIOLA (NCT02734004) trial, which showed increased type I IFN, STING, and JAK/STAT pathway expression following olaparib treatment, in line with preclinical findings. These data together provide evidence for a mechanism and schedule underpinning potential benefit of ICB combination with olaparib.
Topics & Concepts
OlaparibCancer researchImmune systemPARP inhibitorMedicineTumor microenvironmentImmunotherapyDownregulation and upregulationImmunologyPoly ADP ribose polymeraseBiologyGenePolymeraseBiochemistryPARP inhibition in cancer therapyDNA Repair MechanismsCancer Immunotherapy and Biomarkers