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Arg1 expression defines immunosuppressive subsets of immune infiltrating cells in cancer

ABSTRACT: Tumor-associated macrophages (TAM) have attracted attention as they can modulate key cancer-related activities, yet TAM represent a heterogenous group of cells that remain incompletely characterized. In growing tumors, TAM are often referred to as M2-like macrophages, which are cells that display immunosuppressive and tumorigenic functions and express the enzyme arginase 1 (Arg1). Here we combined single cell intravital imaging with scRNA seq to uncover the topography and molecular profiles of Arg1+ macrophages in mice. We further assessed how immunotherapeutic interventions impact these cells directly in vivo. We show that: i) Arg1+ macrophages are more abundant in tumors compared to other organs; ii) there exist two morphologically distinct subsets of Arg1 TAM defined by previously unknown markers (Gbp2b, Bst1, Sgk1, Pmepa1, Ms4a7); iii) anti-Programmed Cell Death-1 (aPD-1) therapy decreases the number of Arg1+ TAM while increasing Arg1– TAM; iv) accordingly, pharmacological inhibition of arginase 1 does not synergize with aPD-1 therapy. Overall, this research defines subsets of immunosuppressive myeloid cells with powerful complementary single cell analytical approaches that pave the way for a more intricate understanding of TAM behavior.

ORGANISM(S): Mus musculus

PROVIDER: GSE112865 | GEO | 2018/12/11

REPOSITORIES: GEO

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Microarray analysis of brain macrophage subsets and peripheral blood monocytes in traumatic brain injury

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Arg1 expression defines immunosuppressive subsets of immune infiltrating cells in cancer

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