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Infiltration by CXC...
Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
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Ardighieri, L (författare)
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Missale, F (författare)
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Bugatti, M (författare)
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visa fler...
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Gatta, LB (författare)
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Pezzali, I (författare)
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Monti, M (författare)
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Gottardi, S (författare)
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Zanotti, L (författare)
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Bignotti, E (författare)
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Ravaggi, A (författare)
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Tognon, G (författare)
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Odicino, F (författare)
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Calza, S (författare)
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Missolo-Koussou, Y (författare)
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Ries, CH (författare)
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Helft, J (författare)
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Vermi, W (författare)
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- 2021-06-18
- 2021
- Engelska.
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 690201-
- Relaterad länk:
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https://www.frontier...
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http://kipublication...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.
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Ardighieri, L
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Missale, F
-
Bugatti, M
-
Gatta, LB
-
Pezzali, I
-
Monti, M
-
visa fler...
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Gottardi, S
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Zanotti, L
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Bignotti, E
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Ravaggi, A
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Tognon, G
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Odicino, F
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Calza, S
-
Missolo-Koussou, ...
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Ries, CH
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Helft, J
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Vermi, W
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visa färre...
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Karolinska Institutet