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Uncovering the Expression Pattern of the Costimulatory Receptors ICOS, 4-1BB, and OX-40 in Exhausted Peripheral and Tumor-Infiltrating Natural Killer Cells from Patients with Cervical Cancer.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Aug 12; Vol. 25 (16). Date of Electronic Publication: 2024 Aug 12. - Publication Year :
- 2024
-
Abstract
- Cervical cancer (CC) poses a significant health burden, particularly in low- and middle-income countries. NK cells play a crucial role against CC; however, they can become exhausted and lose their cytotoxic capacity. This work explores the expression of costimulatory receptors (ICOS, 4-1BB, OX-40) in exhausted NK cells from CC patients. Peripheral blood and tumor biopsies were collected, and flow cytometry was used to evaluate the expression of costimulatory receptors in exhausted NK cells. There is an increase of peripheral exhausted NK cells (PD-1 <superscript>+</superscript> TIGIT <superscript>+</superscript> ) in CC patients; this subpopulation has a selectively increased expression of the costimulatory receptors ICOS and 4-1BB. An exhausted population is also highly increased in tumor-infiltrating NK cells, and it shows a dramatically increased expression of the costimulatory receptors ICOS (>15×) and 4-1BB (>10×) compared to peripheral NK cells. The exhausted cells, both in the periphery and in the tumor infiltrating lymphocytes (TILs), are also more likely than non-exhausted NK cell populations (PD-1 <superscript>-</superscript> TIGIT <superscript>-</superscript> ) to express these costimulatory receptors; increases ranging from 2.0× ICOS, 2.4× 4-1BB, and 2.6× OX-40 in CD56 <superscript>dim</superscript> PBMCs to 1.5× ICOS, 5× 4-1BB, and 10× OX-40 in TILs were found. Our study demonstrates for the first time the increased expression of the costimulatory receptors ICOS, 4-1BB, and OX-40 in peripheral CD56 <superscript>dim</superscript> , CD56 <superscript>bright</superscript> , and tumor-infiltrating NK cells in CC. Targeting these receptors for stimulation could reverse exhaustion and be a promising immunotherapy strategy.
- Subjects :
- Humans
Female
Middle Aged
Adult
OX40 Ligand metabolism
Uterine Cervical Neoplasms immunology
Uterine Cervical Neoplasms metabolism
Uterine Cervical Neoplasms pathology
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Inducible T-Cell Co-Stimulator Protein metabolism
Lymphocytes, Tumor-Infiltrating immunology
Lymphocytes, Tumor-Infiltrating metabolism
Tumor Necrosis Factor Receptor Superfamily, Member 9 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39201462
- Full Text :
- https://doi.org/10.3390/ijms25168775