Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression.

The Journal of Experimental Medicine
Anders EtzerodtToby Lawrence

Abstract

Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable of contributing to antitumor immunity. Recent studies have revealed an unprecedented heterogeneity among TAMs in both human cancer and experimental models. Nevertheless, we still understand little about the contribution of different TAM subsets to tumor progression. Here, we demonstrate that CD163-expressing TAMs specifically maintain immune suppression in an experimental model of melanoma that is resistant to anti-PD-1 checkpoint therapy. Specific depletion of the CD163+ macrophages results in a massive infiltration of activated T cells and tumor regression. Importantly, the infiltration of cytotoxic T cells was accompanied by the mobilization of inflammatory monocytes that significantly contributed to tumor regression. Thus, the specific targeting of CD163+ TAMs reeducates the tumor immune microenvironment and promotes both myeloid and T cell-mediated antitumor immunity, illustrating the importance of selective targeting of tumor-associated myeloid cells in a therapeutic context.

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Citations

Jan 18, 2020·The Journal of Experimental Medicine·Anders EtzerodtToby Lawrence
Jan 31, 2020·International Journal of Cancer. Journal International Du Cancer·Eleonore De GuillebonEric Tartour
Feb 23, 2020·The Journal of Pathology·Tim Beltraminelli, Michele De Palma
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Apr 3, 2020·International Journal of Molecular Sciences·Vera PetrovaViktor Umansky
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Apr 16, 2021·The Journal of Experimental Medicine·Chun I YuKarolina Palucka
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Methods Mentioned

BETA
flow cytometry
PCA
flow
PCR
fluorescence
FACS
confocal microscopy
biopsy
size-exclusion chromatography
dynamic light scattering

Software Mentioned

Fluidigm
GraphPad Prism
Primer
Time PCR Analysis
Morpheus
Qlucore Omics Explorer
- Blast
FlowJo
Fluidigm Biomark
Real

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