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Off-Target and Tumor-Specific Accumulation of Monocytes, Macrophages and Myeloid-Derived Suppressor Cells after Systemic Injection.


ABSTRACT: Solid tumors frequently coexist with a degree of local chronic inflammation. Recruited myeloid cells can therefore be considered as interesting vehicles for tumor-targeted delivery of therapeutic agents. Using in vivo imaging, the short-term accumulation of systemically injected monocytes, macrophages and myeloid-derived suppressor cells (MDSCs) was compared in mice bearing fat pad mammary carcinomas. Monocytes and macrophages demonstrated almost identical in vivo and ex vivo distribution patterns with maximal tumor-associated accumulation seen 48 hours after injection that remained stable over the 4-day follow-up period. However, a substantial accumulation of both cell types was also seen in the liver, spleen and lungs albeit decreasing over time in all three locations. The MDSCs exhibited a similar distribution pattern as the monocytes and macrophages, but demonstrated a better relative on-target fraction over time. Overall, our findings highlight off-target cell accumulation as a major obstacle in the use of myeloid cells as vehicles for therapeutic tumor-targeted agents and indicate that their short-term on-target accumulation is mainly of nonspecific nature.

SUBMITTER: Combes F 

PROVIDER: S-EPMC6076377 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Off-Target and Tumor-Specific Accumulation of Monocytes, Macrophages and Myeloid-Derived Suppressor Cells after Systemic Injection.

Combes Francis F   Mc Cafferty Séan S   Meyer Evelyne E   Sanders Niek N NN  

Neoplasia (New York, N.Y.) 20180718 8


Solid tumors frequently coexist with a degree of local chronic inflammation. Recruited myeloid cells can therefore be considered as interesting vehicles for tumor-targeted delivery of therapeutic agents. Using in vivo imaging, the short-term accumulation of systemically injected monocytes, macrophages and myeloid-derived suppressor cells (MDSCs) was compared in mice bearing fat pad mammary carcinomas. Monocytes and macrophages demonstrated almost identical in vivo and ex vivo distribution patter  ...[more]

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