Speaker
Description
Cancer progression can be understood as the disruption of tissue homeostasis by tumor cells that co-opt their microenvironment\cite{BasantaAnderson2017}. In multiple myeloma (MM), this disruption unfolds within the bone marrow, where stromal cells, osteoclasts, osteoblasts, and immune populations form spatially heterogeneous niches. We have previously shown that integrated computational models of the bone ecosystem can capture how spatial microenvironmental structure shapes cancer-bone interactions\cite{Araujo2014} and how environment-mediated drug resistance (EMDR) in stroma-proximal niches facilitates relapse and clonal heterogeneity\cite{Bishop2024}. Separately, our work on stromal protection in breast cancer demonstrated that stroma-augmented proliferation indirectly drives chemoresistance by accelerating tumor recovery between treatment cycles\cite{Miroshnychenko2023}. Here, we extend our MM bone ecosystem ABM by introducing cytotoxic T-cell and regulatory T-cell (Treg) agents whose activity depends on local microenvironmental conditions. We investigate how spatial niche structure shapes effective anti-myeloma immunity, how Treg-mediated suppression generates local immunosuppressive refugia, and how these dynamics influence evolutionary trajectories under therapy. Our results suggest that spatially homogeneous assumptions about immune function can substantially mischaracterize treatment response, underscoring that niche-specific immune ecology is critical for understanding resistance in MM.
Bibliography
@article{Araujo2014,
author = {Araujo, Arturo and Cook, Leah M. and Lynch, Conor C. and Basanta, David},
title = {An integrated computational model of the bone microenvironment in bone-metastatic prostate cancer},
journal = {Cancer Research},
volume = {74},
number = {9},
pages = {2391--2401},
year = {2014},
doi = {10.1158/0008-5472.CAN-13-2652}
}
@article{BasantaAnderson2017,
author = {Basanta, David and Anderson, Alexander R. A.},
title = {Homeostasis back and forth: an ecoevolutionary perspective of cancer},
journal = {Cold Spring Harbor Perspectives in Medicine},
volume = {7},
number = {9},
pages = {a028332},
year = {2017},
doi = {10.1101/cshperspect.a028332}
}
@article{Miroshnychenko2023,
author = {Miroshnychenko, Daria and Miti, Tatiana and Kumar, Pragya and Miller, Anna and Laurie, Mark and Giraldo, Nathalia and Bui, Marilyn M. and Altrock, Philipp M. and Basanta, David and Marusyk, Andriy},
title = {Stroma-mediated breast cancer cell proliferation indirectly drives chemoresistance by accelerating tumor recovery between chemotherapy cycles},
journal = {Cancer Research},
volume = {83},
number = {22},
pages = {3681--3692},
year = {2023},
doi = {10.1158/0008-5472.CAN-23-0398}
}
@article{Bishop2024,
author = {Bishop, Ryan T. and Miller, Anna K. and Froid, Matthew and others},
title = {The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease},
journal = {Nature Communications},
volume = {15},
pages = {2458},
year = {2024},
doi = {10.1038/s41467-024-46594-0}
}
