ILT4 in Colorectal Cancer Cells Induces Suppressive T Cell Contexture and Disease Progression.
IFN-γ
T cell subsets
colorectal cancer
immunoglobulin-like transcript 4
immunosuppression
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2021
2021
Historique:
received:
09
11
2020
accepted:
16
06
2021
entrez:
29
7
2021
pubmed:
30
7
2021
medline:
30
7
2021
Statut:
epublish
Résumé
Immune checkpoint blockade (ICB) therapy shows little or no clinical benefit in most colorectal cancer (CRC) patients, due to the immunosuppressive T cell contexture in the tumor microenvironment (TME). Immunoglobulin-like transcript (ILT) 4 is an immunosuppressive molecule in myeloid cells. ILT4 is enriched in solid tumor cells, facilitating their proliferation, invasion, and metastasis. However, the regulatory role of ILT4 in T cell immunity of CRC is still undetermined. Here, we aimed to explore how tumor cell-derived ILT4 orchestrates T cell infiltration, subset distribution, and function in CRC. A total of 145 paraffin-embedded cancer tissues and the corresponding clinicopathological information were collected from CRC patients. Immunohistochemical (IHC) staining and public database analyses determined the correlation of ILT4 expression with different T cell subset densities, IFN-γ levels, and patient outcomes. Paired Ig-like receptor B (PIR-B, ILT4 mouse ortholog)-overexpressing/-downregulated MC38 cells were subcutaneously injected into C57BL/6 mice as a CRC transplantation model. The frequencies, subsets, and IFN-γ levels of T cells in mouse blood and spleens were determined using flow cytometry and immunohistochemistry, respectively. High ILT4 expression in CRC cells was associated with decreased T cell infiltration, disease progression, and poor patient survival. T cell subset analyses indicated that ILT4-high patients showed reduced CD8 ILT4 in CRC cells induced immunosuppressive T cell subset infiltration and impaired IFN-γ production in TILs, suggesting that ILT4 might be a potential immunotherapeutic target and prognostic biomarker.
Identifiants
pubmed: 34321889
doi: 10.2147/OTT.S290348
pii: 290348
pmc: PMC8312509
doi:
Types de publication
Journal Article
Langues
eng
Pagination
4239-4254Informations de copyright
© 2021 Yang et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflict of interest.
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