Cancer cell plasticity and MHC-II-mediated immune tolerance promote breast cancer metastasis to lymph nodes.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 09 2023
04 09 2023
Historique:
received:
28
10
2022
revised:
10
04
2023
accepted:
25
05
2023
pmc-release:
21
12
2023
medline:
23
6
2023
pubmed:
21
6
2023
entrez:
21
6
2023
Statut:
ppublish
Résumé
Tumor-draining lymph nodes (TDLNs) are important for tumor antigen-specific T cell generation and effective anticancer immune responses. However, TDLNs are often the primary site of metastasis, causing immune suppression and worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer cell heterogeneity, plasticity, and immune evasion during breast cancer progression and lymph node metastasis (LNM). A subset of cancer cells in the lymph nodes exhibited elevated MHC class II (MHC-II) gene expression in both mice and humans. MHC-II+ cancer cells lacked costimulatory molecule expression, leading to regulatory T cell (Treg) expansion and fewer CD4+ effector T cells in TDLNs. Genetic knockout of MHC-II reduced LNM and Treg expansion, while overexpression of the MHC-II transactivator, Ciita, worsened LNM and caused excessive Treg expansion. These findings demonstrate that cancer cell MHC-II expression promotes metastasis and immune evasion in TDLNs.
Identifiants
pubmed: 37341991
pii: 214183
doi: 10.1084/jem.20221847
pmc: PMC10286805
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL007627
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA251062
Pays : United States
Organisme : NCI NIH HHS
ID : K22 CA230315
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI097745
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128168
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA275298
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA284372
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA284603
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214913
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA234940
Pays : United States
Informations de copyright
© 2023 Lei et al.
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