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Cellular and molecular identity of tumor-associated macrophages in glioblastoma

Abstract: In glioblastoma (GBM), tumor-associated macrophages (TAM) represent up to one half of the cells of the tumor mass, including both infiltrating macrophages and resident brain microglia. In an effort to delineate the temporal and spatial dynamics of TAM composition during gliomagenesis, we used genetically engineered and GL261-induced mouse models in combination with CX3CR1GFP/WT;CCR2RFP/WT double knock-in mice. Using this approach, we demonstrated that CX3CR1LoCCR2Hi monocytes were recruited to the GBM, where they transitioned to CX3CR1HiCCR2Lo macrophages and CX3CR1HiCCR2- microglia-like cells. Infiltrating macrophages/monocytes constituted approximately 85% of the total TAM population, with resident microglia accounting for the approximately 15% remaining. Bone marrow-derived infiltrating macrophages/monocytes were recruited to the tumor early during GBM initiation, where they localized preferentially to perivascular areas. In contrast, resident microglia were localized mainly to peritumoral regions. RNA-sequencing analyses revealed differential gene expression patterns unique to infiltrating and resident cells, suggesting unique functions for each TAM population. Notably, limiting monocyte infiltration via genetic Ccl2 reduction prolonged the survival of tumor-bearing mice. Our findings illuminate the unique composition and functions of infiltrating and resident myeloid cells in GBM, establishing a rationale to target infiltrating cells in this neoplasm.

 Fuente: Cancer Research, 2017, 77(9), 2266-2278

 Editorial: American Association for Cancer Research

 Año de publicación: 2017

 Nº de páginas: 14

 Tipo de publicación: Artículo de Revista

 DOI: 10.1158/0008-5472.CAN-16-2310

 ISSN: 0008-5472,1538-7445

 Url de la publicación: https://www.doi.org/10.1158/0008-5472.CAN-16-2310

Autoría

CHEN, ZHIHONG

FENG, XI

HERTING, CAMERON J

NIE, KAI

PONG, WINNIE W

RASMUSSEN, RIKKE

DWIVEDI, BHAKTI

SEBY, SANDRA

WOLF, SUSANNE A

GUTMANN, DAVID H

HAMBARDZUMYAN, DOLORES