Abstract
Tumor associated macrophages (TAMs) are a highly plastic stromal cell type which are exquisitely polarized by the tumor microenvironment to support cancer progression1, 2. Single-cell RNA-sequencing (scRNA-seq) of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT) identified three distinct polarization trajectories for these cells within the tumor microenvironment. We reveal sub-divisions within the pro-tumoral TAM population with one subset expressing Lyve-1 and residing in a spatial niche proximal to blood vasculature within the tumor. We demonstrate that selective depletion of the Lyve-1+ TAM population significantly slows tumor growth because of a non-redundant role of these cells in orchestrating the platelet derived growth factor-CC (PDGF-CC)-dependent expansion of tumor-resident pericytes which underpins vasculature growth and development. This study uncovers that local pericyte expansion in cancer is not an autonomous event but tightly regulated by the perivascular Lyve-1+ TAM population, which ultimately govern the success of angiogenesis in cancer.
Competing Interest Statement
The authors have declared no competing interest.