Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets

Luca Cassetta; Stamatina Fragkogianni; Andrew H. Sims; Agnieszka Swierczak; Lesley M. Forrester; Hui Zhang; Daniel Soong; Tiziana Cotechini; Pavana Anur; Elaine Lin; Antonella Fidanza; Martha Lopez Yrigoyen; Michael Millar; Alexandra Urman; Zhichao Ai; Paul T. Spellman; E. Shelley Hwang; J Michael Dixon; Lisa Wiechmann; Lisa M  Coussens; Harriet W. Smith; Jeffrey W. Pollard

doi:10.1016/j.ccell.2019.02.009

Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets

Luca Cassetta, Stamatina Fragkogianni, Andrew H. Sims, Agnieszka Swierczak, Lesley M. Forrester, Hui Zhang, Daniel Soong, Tiziana Cotechini, Pavana Anur, Elaine Lin, Antonella Fidanza, Martha Lopez Yrigoyen, Michael Millar, Alexandra Urman, Zhichao Ai, Paul T. Spellman, E. Shelley Hwang, J Michael Dixon, Lisa Wiechmann, Lisa M CoussensHarriet W. Smith, Jeffrey W. Pollard

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.

Original language	English
Pages (from-to)	588-602.e10
Number of pages	25
Journal	Cancer Cell
Volume	35
Issue number	4
Early online date	28 Mar 2019
DOIs	https://doi.org/10.1016/j.ccell.2019.02.009
Publication status	Published - 15 Apr 2019

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10.1016/j.ccell.2019.02.009Licence: Creative Commons: Attribution (CC-BY)

CANCER-CELL-accepted - J PollardAccepted author manuscript, 4.88 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

https://www.sciencedirect.com/science/article/pii/S1535610819301047?via%3DihubLicence: Creative Commons: Attribution (CC-BY)

MRC Centre for Reproductive Health at the University of Edinburgh
Pollard, J.
MRC
12/09/16 → 11/09/22
Project: Research
The metastatic cascade: macrophages lead the way
Pollard, J.
UK-based charities
1/10/13 → 30/06/21
Project: Research

Lesley Forrester
- Deanery of Clinical Sciences - UoE Retired Staff
- Centre for Regenerative Medicine
- Centre for Inflammation Research
- Edinburgh Haematopoiesis Network
Person: Academic: Research Active , Affiliated Independent Researcher

Cite this

Cassetta, L., Fragkogianni, S., Sims, A. H., Swierczak, A., Forrester, L. M., Zhang, H., Soong, D., Cotechini, T., Anur, P., Lin, E., Fidanza, A., Lopez Yrigoyen, M., Millar, M., Urman, A., Ai, Z., Spellman, P. T., Hwang, E. S., Dixon, J. M., Wiechmann, L., ... Pollard, J. W. (2019). Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets. Cancer Cell, 35(4), 588-602.e10. https://doi.org/10.1016/j.ccell.2019.02.009

@article{63a217b434e84d02bf6d794aa17da8df,

title = "Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets",

abstract = "The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.",

author = "Luca Cassetta and Stamatina Fragkogianni and Sims, {Andrew H.} and Agnieszka Swierczak and Forrester, {Lesley M.} and Hui Zhang and Daniel Soong and Tiziana Cotechini and Pavana Anur and Elaine Lin and Antonella Fidanza and {Lopez Yrigoyen}, Martha and Michael Millar and Alexandra Urman and Zhichao Ai and Spellman, {Paul T.} and Hwang, {E. Shelley} and Dixon, {J Michael} and Lisa Wiechmann and Coussens, {Lisa M} and {W. Smith}, Harriet and Pollard, {Jeffrey W.}",

year = "2019",

month = apr,

day = "15",

doi = "10.1016/j.ccell.2019.02.009",

language = "English",

volume = "35",

pages = "588--602.e10",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

}

Cassetta, L, Fragkogianni, S, Sims, AH, Swierczak, A, Forrester, LM, Zhang, H, Soong, D, Cotechini, T, Anur, P, Lin, E, Fidanza, A, Lopez Yrigoyen, M, Millar, M, Urman, A, Ai, Z, Spellman, PT, Hwang, ES, Dixon, JM, Wiechmann, L, Coussens, LM, W. Smith, H & Pollard, JW 2019, 'Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets', Cancer Cell, vol. 35, no. 4, pp. 588-602.e10. https://doi.org/10.1016/j.ccell.2019.02.009

TY - JOUR

T1 - Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets

AU - Cassetta, Luca

AU - Fragkogianni, Stamatina

AU - Sims, Andrew H.

AU - Swierczak, Agnieszka

AU - Forrester, Lesley M.

AU - Zhang, Hui

AU - Soong, Daniel

AU - Cotechini, Tiziana

AU - Anur, Pavana

AU - Lin, Elaine

AU - Fidanza, Antonella

AU - Lopez Yrigoyen, Martha

AU - Millar, Michael

AU - Urman, Alexandra

AU - Ai, Zhichao

AU - Spellman, Paul T.

AU - Hwang, E. Shelley

AU - Dixon, J Michael

AU - Wiechmann, Lisa

AU - Coussens, Lisa M

AU - W. Smith, Harriet

AU - Pollard, Jeffrey W.

PY - 2019/4/15

Y1 - 2019/4/15

N2 - The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.

AB - The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.

U2 - 10.1016/j.ccell.2019.02.009

DO - 10.1016/j.ccell.2019.02.009

M3 - Article

SN - 1535-6108

VL - 35

SP - 588-602.e10

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets

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Projects

MRC Centre for Reproductive Health at the University of Edinburgh

The metastatic cascade: macrophages lead the way

Profiles

Lesley Forrester

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