Details

Autor(en) / Beteiligte

• Ardighieri, Laura
• Missale, Francesco
• Bugatti, Mattia
• Gatta, Luisa Benerini
• Pezzali, Irene
• Monti, Matilde
• Gottardi, Stefano
• Zanotti, Laura
• Bignotti, Eliana
• Ravaggi, Antonella
• Tognon, Germana
• Odicino, Franco
• Calza, Stefano
• Missolo-Koussou, Yoann
• Ries, Carola Hermine
• Helft, Julie
• Vermi, William

Titel

Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes

Ist Teil von

• Frontiers in immunology, 2021-06, Vol.12, p.690201-690201

Ort / Verlag

Frontiers Media S.A

Erscheinungsjahr

2021

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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-IS 30 ) 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.