Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
| العنوان: | Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes |
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| المؤلفون: | Laura Ardighieri, Francesco Missale, Mattia Bugatti, Luisa Benerini Gatta, Irene Pezzali, Matilde Monti, Stefano Gottardi, Laura Zanotti, Eliana Bignotti, Antonella Ravaggi, Germana Tognon, Franco Odicino, Stefano Calza, Yoann Missolo-Koussou, Carola Hermine Ries, Julie Helft, William Vermi |
| المصدر: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, CD3 Complex, 0302 clinical medicine, Tumor-Associated Macrophages, Tumor Microenvironment, Immunology and Allergy, Receptors, Immunologic, Cells, Cultured, Original Research, Ovarian Neoplasms, Membrane Glycoproteins, biology, Antigen processing, CXCL10, Middle Aged, Prognosis, Serous fluid, medicine.anatomical_structure, Phenotype, STAT1 Transcription Factor, ovarian cancer, 030220 oncology & carcinogenesis, Female, signature, CD3, T cell, Immunology, Antigens, Differentiation, Myelomonocytic, Receptors, Cell Surface, macrophage, 03 medical and health sciences, Immune system, Lymphocytes, Tumor-Infiltrating, Antigens, CD, medicine, Humans, Aged, polarization, business.industry, Carcinoma, RC581-607, medicine.disease, Chemokine CXCL10, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, biology.protein, Immunologic diseases. Allergy, Ovarian cancer, business, Neoplasms, Cystic, Mucinous, and Serous, CD163, Interferon Regulatory Factor-1 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c588013163420c866e780448acdfefbTest https://www.frontiersin.org/articles/10.3389/fimmu.2021.690201/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5c588013163420c866e780448acdfefb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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