Sökning: WFRF:(Karlsson Patrick)
> (2020-2024) >
Targeting MARCO and...
Targeting MARCO and IL-37R on immunosuppressive macrophages in lung cancer blocks regulatory T cells and supports cytotoxic lymphocyte function
-
- La Fleur, Linnea (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Johan Botling
-
- Botling, Johan (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Johan Botling
-
He, Fei (författare)
-
visa fler...
-
Pelicano, Catarina (författare)
-
- Zhou, Chikai (författare)
- Karolinska Institutet
-
He, Chenfei (författare)
-
- Palano, Giorgia (författare)
- Karolinska Institutet
-
- Mezheyeuski, Artur (författare)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
-
- Micke, Patrick (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Patrick Micke
-
Ravetch, Jeffrey V (författare)
-
- Karlsson, Mikael C I (författare)
- Karolinska Institutet
-
- Sarhan, Dhifaf (författare)
- Karolinska Institutet
-
visa färre...
-
(creator_code:org_t)
- American Association For Cancer Research (AACR), 2021
- 2021
- Engelska.
-
Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:4, s. 956-967
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- The progression and metastatic capacity of solid tumors are strongly influenced by immune cells in the tumor microenvironment. In non-small cell lung cancer (NSCLC), accumulation of anti-inflammatory tumor-associated macrophages (TAMs) is associated with worse clinical outcome and resistance to therapy. Here we investigated the immune landscape of NSCLC in the presence of pro-tumoral TAMs expressing the macrophage receptor with collagenous structure (MARCO). MARCO-expressing TAM numbers correlated with increased occurrence of regulatory T cells and effector T cells and decreased Natural Killer (NK) cells in these tumors. Furthermore, transcriptomic data from the tumors uncovered a correlation between MARCO expression and the anti-inflammatory cytokine IL-37. In vitro studies subsequently showed that lung cancer cells polarized macrophages to express MARCO and gain an immune-suppressive phenotype through the release of IL-37. MARCO-expressing TAMs blocked cytotoxic T cell and NK cell activation, inhibiting their proliferation, cytokine production, and tumor killing capacity. Mechanistically, MARCO+ macrophages enhanced regulatory T (Treg) cell proliferation and IL-10 production and diminished CD8 T cell activities. Targeting MARCO or IL-37 receptor (IL-37R) by antibody or CRISPR knockout of IL-37 in lung cancer cell lines repolarized TAMs, resulting in recovered cytolytic activity and anti-tumoral capacity of NK cells and T cells and down-modulated Treg cell activities. In summary, our data demonstrate a novel immune therapeutic approach targeting human TAMs immune suppression of NK and T cell anti-tumor activities.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Nyckelord
- Pathology
- Patologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
La Fleur, Linnea
-
Botling, Johan
-
He, Fei
-
Pelicano, Catari ...
-
Zhou, Chikai
-
He, Chenfei
-
visa fler...
-
Palano, Giorgia
-
Mezheyeuski, Art ...
-
Micke, Patrick
-
Ravetch, Jeffrey ...
-
Karlsson, Mikael ...
-
Sarhan, Dhifaf
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Klinisk laborato ...
- Artiklar i publikationen
-
Cancer Research
- Av lärosätet
-
Uppsala universitet
-
Karolinska Institutet