A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
08 Mar 2022
08 Mar 2022
Historique:
received:
08
12
2021
accepted:
11
02
2022
revised:
03
02
2022
entrez:
9
3
2022
pubmed:
10
3
2022
medline:
10
3
2022
Statut:
epublish
Résumé
Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as αPD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.Here, an assessment of the immune landscape in the tumor microenvironment (TME) of two TNBC mouse models has been performed using single-cell RNA sequencing technology. Specifically, immune cells were evaluated in untreated conditions and after treatments with chemotherapy or immunotherapy used as single agents or in combination. A decrease of Treg was found in treatments with in vivo efficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy and an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were enriched in treatments with low efficacy while M1-like macrophages followed an opposite trend. For both models, similar proportions of B cells were detected with an increase of proliferative B cells in treatments involving cisplatin in combination with αPD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC.
Identifiants
pubmed: 35260564
doi: 10.1038/s41420-022-00893-x
pii: 10.1038/s41420-022-00893-x
pmc: PMC8904804
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)
ID : IG20109
Informations de copyright
© 2022. The Author(s).
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