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Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer

La Fleur, Linnéa ; Boura, Vanessa F ; Alexeyenko, Andrey ; Berglund, Anders ; Pontén, Victor ; Mattsson, Johanna S M ; Djureinovic, Dijana ; Persson, Johan ; Brunnström, Hans LU orcid and Isaksson, Johan , et al. (2018) In International Journal of Cancer 143(7). p.1741-1752
Abstract

Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n = 352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n = 199) with available RNA-seq data. We observed a large variation in macrophage... (More)

Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n = 352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n = 199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
143
issue
7
pages
1741 - 1752
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:29667169
  • scopus:85047397636
ISSN
0020-7136
DOI
10.1002/ijc.31545
language
English
LU publication?
yes
additional info
© 2018 UICC.
id
3856ddcd-c563-4e61-9840-c2dd586213e9
date added to LUP
2019-05-27 21:30:04
date last changed
2024-06-11 14:27:38
@article{3856ddcd-c563-4e61-9840-c2dd586213e9,
  abstract     = {{<p>Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n = 352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n = 199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.</p>}},
  author       = {{La Fleur, Linnéa and Boura, Vanessa F and Alexeyenko, Andrey and Berglund, Anders and Pontén, Victor and Mattsson, Johanna S M and Djureinovic, Dijana and Persson, Johan and Brunnström, Hans and Isaksson, Johan and Brandén, Eva and Koyi, Hirsh and Micke, Patrick and Karlsson, Mikael C I and Botling, Johan}},
  issn         = {{0020-7136}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{7}},
  pages        = {{1741--1752}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer}},
  url          = {{http://dx.doi.org/10.1002/ijc.31545}},
  doi          = {{10.1002/ijc.31545}},
  volume       = {{143}},
  year         = {{2018}},
}