Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer

Autor: Hayri E. Balcioglu, Iris Nederlof, Mieke Timmermans, John W.M. Martens, Reno Debets, Renée Foekens, Olga I. Isaeva, Rebecca Wijers, Hugo M. Horlings, Marcel Smid, Anita M. A. C. Trapman-Jansen, Dora Hammerl, Roberto Salgado, Leonie Voorwerk, Marleen Kok
Přispěvatelé: Medical Oncology
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Adult
T-Lymphocytes
Science
T cell
Programmed Cell Death 1 Receptor
Immunology
Cell
Antigens
Differentiation
Myelomonocytic
Datasets as Topic
General Physics and Astronomy
Receptors
Cell Surface
Triple Negative Breast Neoplasms
Diseases
Biology
Article
General Biochemistry
Genetics and Molecular Biology
Immunophenotyping
Cohort Studies
Lymphocytes
Tumor-Infiltrating
Medical research
Immune system
SDG 3 - Good Health and Well-being
Antigens
CD
Tumor Microenvironment
medicine
Humans
Breast
RNA-Seq
Receptor
Immune Checkpoint Inhibitors
Wnt Signaling Pathway
Mastectomy
Triple-negative breast cancer
Cancer
Spatial Analysis
Multidisciplinary
T-cell receptor
Wnt signaling pathway
General Chemistry
Prognosis
Phenotype
Neoadjuvant Therapy
medicine.anatomical_structure
Drug Resistance
Neoplasm
Cancer research
Female
Tumor Escape
Biomarkers
Zdroj: Nature Communications, 12(1):5668. Nature Publishing Group
Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021)
Nature Communications
ISSN: 2041-1723
Popis: Only a subgroup of triple-negative breast cancer (TNBC) responds to immune checkpoint inhibitors (ICI). To better understand lack of response to ICI, we analyze 681 TNBCs for spatial immune cell contextures in relation to clinical outcomes and pathways of T cell evasion. Excluded, ignored and inflamed phenotypes can be captured by a gene classifier that predicts prognosis of various cancers as well as anti-PD1 response of metastatic TNBC patients in a phase II trial. The excluded phenotype, which is associated with resistance to anti-PD1, demonstrates deposits of collagen-10, enhanced glycolysis, and activation of TGFβ/VEGF pathways; the ignored phenotype, also associated with resistance to anti-PD1, shows either high density of CD163+ myeloid cells or activation of WNT/PPARγ pathways; whereas the inflamed phenotype, which is associated with response to anti-PD1, revealed necrosis, high density of CLEC9A+ dendritic cells, high TCR clonality independent of neo-antigens, and enhanced expression of T cell co-inhibitory receptors.
Only a subset of triple negative breast cancer patients respond to immunotherapy. Here, the authors analysed spatial immune contextures, which can be captured by a gene classifier, in relation to genomic alterations, mechanisms of T cell evasion and response to anti-PD1 treatment.
Databáze: OpenAIRE
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