Quantitative MRI cell tracking of immune cell recruitment to tumors and draining lymph nodes in response to anti-PD-1 and a DPX-based immunotherapy.

Autor:	Tremblay ML; Biomedical Translational Imaging Centre (BIOTIC, IWK Health Centre, Halifax, NS, Canada.; Dalhousie University, Halifax, NS, Canada.; IMV Inc, Halifax, NS, Canada., O'Brien-Moran Z; Biomedical Translational Imaging Centre (BIOTIC, IWK Health Centre, Halifax, NS, Canada.; Department of Physics, Dalhousie University, Halifax, NS, Canada., Rioux JA; Biomedical Translational Imaging Centre (BIOTIC, IWK Health Centre, Halifax, NS, Canada.; Department of Physics, Dalhousie University, Halifax, NS, Canada.; Department of Diagnostic Radiology, Dalhousie University, Halifax, NS, Canada., Nuschke A; Biomedical Translational Imaging Centre (BIOTIC, IWK Health Centre, Halifax, NS, Canada., Davis C; Biomedical Translational Imaging Centre (BIOTIC, IWK Health Centre, Halifax, NS, Canada., Kast WM; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Weir G; IMV Inc, Halifax, NS, Canada., Stanford M; Dalhousie University, Halifax, NS, Canada.; IMV Inc, Halifax, NS, Canada., Brewer KD; Biomedical Translational Imaging Centre (BIOTIC, IWK Health Centre, Halifax, NS, Canada.; Dalhousie University, Halifax, NS, Canada.; Department of Physics, Dalhousie University, Halifax, NS, Canada.; Department of Diagnostic Radiology, Dalhousie University, Halifax, NS, Canada.; School of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2020 Nov 29; Vol. 9 (1), pp. 1851539. Date of Electronic Publication: 2020 Nov 29.
DOI:	10.1080/2162402X.2020.1851539
Abstrakt:	DPX is a unique T cell activating formulation that generates robust immune responses (both clinically and preclinically) which can be tailored to various cancers via the use of tumor-specific antigens and adjuvants. While DPX-based immunotherapies may act complementary with checkpoint inhibitors, combination therapy is not always easily predictable based on individual therapeutic responses. Optimizing these combinations can be improved by understanding the mechanism of action underlying the individual therapies. Magnetic Resonance Imaging (MRI) allows tracking of cells labeled with superparamagnetic iron oxide (SPIO), which can yield valuable information about the localization of crucial immune cell subsets. In this work, we evaluated the use of a multi-echo, single point MRI pulse sequence, TurboSPI, for tracking and quantifying cytotoxic T lymphocytes (CTLs) and myeloid lineage cells (MLCs). In a subcutaneous cervical cancer model (C3) we compared untreated mice to mice treated with either a single therapy (anti-PD-1 or DPX-R9F) or a combination of both therapies. We were able to detect, using TurboSPI, significant increases in CTL recruitment dynamics in response to combination therapy. We also observed differences in MLC recruitment to therapy-draining (DPX-R9F) lymph nodes in response to treatment with DPX-R9F (alone or in combination with anti-PD-1). We demonstrated that the therapies presented herein induced time-varying changes in cell recruitment. This work establishes that these quantitative molecular MRI techniques can be expanded to study a number of cancer and immunotherapy combinations to improve our understanding of longitudinal immunological changes and mechanisms of action. Competing Interests: At the time of writing this manuscript, MLT, GW, and MS were employees of IMV Inc., who manufactures DPX-based immunotherapies. KDB also had a research contract with IMV for an unrelated project. (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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