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).

Methods: Here we combined high resolution intravital imaging with single cell RNA seq to uncover the topography and molecular profiles of immunosuppressive macrophages in mice. We further assessed how immunotherapeutic interventions impact these cells directly in vivo.

Results: 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.

Conclusion: Overall, this research shows how powerful complementary single cell analytical approaches can be used to improve our understanding of drug action in vivo.

Keywords: immunotherapy, cancer, PD1, macrophage, arginase

肿瘤相关巨噬细胞（TAM）可以调节关键的癌症相关活性，因此引起了人们的关注，但TAM代表了一组异质性细胞，其特征尚不完全。在生长中的肿瘤中，TAM通常被称为M2样巨噬细胞，是具有免疫抑制和致瘤功能并表达精氨酸酶1（Arg1）的细胞。

方法：在这里，我们将高分辨率的活体成像与单细胞RNA序列相结合，以揭示小鼠免疫抑制巨噬细胞的形貌和分子特征。我们进一步评估了免疫治疗干预如何直接在体内影响这些细胞。

结果：我们表明：i）Arg1 +巨噬细胞在肿瘤中比其他器官更为丰富；ii）存在由先前未知的标记（Gbp2b，Bst1，Sgk1，Pmepa1，Ms4a7）定义的Arg1 TAM的两个形态学上不同的子集；iii）抗程序性细胞死亡1（aPD-1）治疗可减少Arg1 + TAM的数量，同时增加Arg1- TAM；iv）因此，精氨酸酶1的药理抑制作用与aPD-1治疗没有协同作用。

结论：总的来说，这项研究表明如何使用功能强大的互补单细胞分析方法来增进我们对体内药物作用的了解。

关键词：免疫治疗，癌症，PD1，巨噬细胞，精氨酸酶