Mesenchymal ovarian cancer cells promote CD8+ T cell exhaustion through the LGALS3-LAG3 axis

Cancer cells often metastasize by undergoing an epithelial-mesenchymal transition (EMT). Although abundance of CD8 + T-cells in the tumor microenvironment correlates with improved survival, mesenchymal cancer cells acquire greater resistance to antitumor immunity in some cancers. We hypothesized the...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:NPJ systems biology and applications Ročník 9; číslo 1; s. 61 - 17
Hlavní autoři: Yakubovich, Edward, Cook, David P., Rodriguez, Galaxia M., Vanderhyden, Barbara C.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 12.12.2023
Nature Publishing Group
Nature Portfolio
Témata:
631/114
631/250
631/553/2711
631/67
Bioinformatics
Biomedical and Life Sciences
CD8 antigen
CD8-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - pathology
Computational Biology/Bioinformatics
Computer Appl. in Life Sciences
Female
Galectin 3 - genetics
Galectin 3 - metabolism
Humans
Immunity
Inflammation
Life Sciences
Lymphocytes
Lymphocytes T
Mesenchyme
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Systems Biology
T-Cell Exhaustion
Tumor Microenvironment
Tumors
ISSN:2056-7189, 2056-7189
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Cancer cells often metastasize by undergoing an epithelial-mesenchymal transition (EMT). Although abundance of CD8 + T-cells in the tumor microenvironment correlates with improved survival, mesenchymal cancer cells acquire greater resistance to antitumor immunity in some cancers. We hypothesized the EMT modulates the immune response to ovarian cancer. Here we show that cancer cells from infiltrated/inflamed tumors possess more mesenchymal cells, than excluded and desert tumors. We also noted high expression of LGALS3 is associated with EMT in vivo, a finding validated with in vitro EMT models. Dissecting the cellular communications among populations in the tumor revealed that mesenchymal cancer cells in infiltrated tumors communicate through LGALS3 to LAG3 receptor expressed by CD8 + T cells. We found CD8 + T cells express high levels of LAG3 , a marker of T cell exhaustion. The results indicate that EMT in ovarian cancer cells promotes interactions between cancer cells and T cells through the LGALS3 - LAG3 axis, which could increase T cell exhaustion in infiltrated tumors, dampening antitumor immunity.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2056-7189
2056-7189
DOI:10.1038/s41540-023-00322-4