An in vivo platform to jointly monitor cellular and metabolic responses to chemotherapy.

Pister, V.; Tatarova, Z.; Park, N.; Gaidhani, G.; Jakubik, J.; Heiser, L.; Blum, J.; Palmiotti, A.; Maloney, E.; Fraenkel, E.; Davidson, S.; Jonas, O.

doi:10.64898/2026.06.25.734296

bioRxiv · 10.64898/2026.06.25.734296

An in vivo platform to jointly monitor cellular and metabolic responses to chemotherapy.

Pister, V.·Tatarova, Z.·Park, N.·Gaidhani, G.·Jakubik, J.·Heiser, L.·Blum, J.·Palmiotti, A.·Maloney, E.·Fraenkel, E.·Davidson, S.·Jonas, O.

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Abstract

How drug treatments reshape immune and metabolic states within intact tumors remains difficult to study with existing methods. We introduce a spatial pharmacology platform that enables parallel analysis of multiple agents within a single tumor, linking local drug exposure to immune and metabolic remodeling. Using a microdevice for localized drug delivery, we created a large-scale paired CyCIF-MALDI dataset spanning 1.5 million cells across 27 MMTV-PyMT tumor sections and nine treatment programs, enabling integrated spatial pharmacology at unprecedented scale. Metabolic signatures robustly predict proteomic spatial neighborhoods establishing metabolism as a powerful predictor of tumor organization and immune phenotype. Within this framework, we identify a dominant metabolic axis defined by the myeloid polarization between CSF1R+ tumor-associated macrophages and MPO+ infiltrating myeloid cells localized near regions of drug-induced tumor cell death. Finally, we detect putative lipid-associated macrophage (LAM)-like populations within drug-resistant treatment regions.

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Pister, V., Tatarova, Z., Park, N., Gaidhani, G., Jakubik, J., Heiser, L., Blum, J., Palmiotti, A., Maloney, E., Fraenkel, E., Davidson, S., Jonas, O.. 2026-06-26. An in vivo platform to jointly monitor cellular and metabolic responses to chemotherapy.. https://doi.org/10.64898/2026.06.25.734296

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