Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer.
Adult
Antigens, CD
/ metabolism
Antigens, Differentiation, Myelomonocytic
/ metabolism
Breast
/ immunology
Cohort Studies
Datasets as Topic
Drug Resistance, Neoplasm
/ immunology
Female
Humans
Immune Checkpoint Inhibitors
/ pharmacology
Immunophenotyping
Lymphocytes, Tumor-Infiltrating
/ immunology
Mastectomy
Neoadjuvant Therapy
/ methods
Prognosis
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
RNA-Seq
Receptors, Cell Surface
/ metabolism
Spatial Analysis
T-Lymphocytes
/ immunology
Triple Negative Breast Neoplasms
/ immunology
Tumor Escape
Tumor Microenvironment
/ drug effects
Wnt Signaling Pathway
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 09 2021
27 09 2021
Historique:
received:
02
06
2020
accepted:
07
09
2021
entrez:
28
9
2021
pubmed:
29
9
2021
medline:
24
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34580291
doi: 10.1038/s41467-021-25962-0
pii: 10.1038/s41467-021-25962-0
pmc: PMC8476574
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, Myelomonocytic
0
CD163 antigen
0
Immune Checkpoint Inhibitors
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5668Informations de copyright
© 2021. The Author(s).
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