Format

Send to

Choose Destination
Immunity. 2014 Nov 20;41(5):815-29. doi: 10.1016/j.immuni.2014.09.014. Epub 2014 Oct 30.

Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression.

Author information

1
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, Singapore 138648, Singapore.
2
Laboratory of Myeloid Cell Immunology, VIB, Brussels 1050, Belgium; Cellular and Molecular Immunology Lab, Vrije Universiteit Brussel, Brussels 1050, Belgium.
3
Department of Urology, National University Health System, Lower Kent Ridge Road, Singapore 119074, Singapore.
4
Department of Pathology, National University Health System, Lower Kent Ridge Road, Singapore 119074, Singapore.
5
Department of Haematology-Oncology, National University Health System, Lower Kent Ridge Road, Singapore 119074, Singapore.
6
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, Singapore 138648, Singapore. Electronic address: subhra_biswas@immunol.a-star.edu.sg.

Abstract

Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. We used molecular profiling combined with functional assays to investigate the role of these cells in human renal cell carcinoma (RCC). Blood monocytes from RCC patients displayed a tumor-promoting transcriptional profile that supported functions like angiogenesis and invasion. Induction of this protumor phenotype required an interleukin-1 receptor (IL-1R)-dependent mechanism. Indeed, targeting of IL-1-IL-1R axis in a human RCC xenograft model abrogated the protumor phenotype of tumor-associated macrophages (TAMs) and reduced tumor growth in vivo. Supporting this, meta-analysis of gene expression from human RCC tumors showed IL1B expression to correlate with myelomonocytic markers, protumor genes, and tumor staging. Analyzing RCC patient tumors confirmed the protumor phenotype of TAMs. These data provide direct evidence for a tumor-promoting role of monocytes and macrophages in human cancer and indicate IL-1-IL-1R as a possible therapeutic target.

PMID:
25453823
DOI:
10.1016/j.immuni.2014.09.014
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center