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NK cells in pancreatic cancer demonstrate impaired cytotoxicity and a regulatory IL-10 phenotype
- Source :
- Oncoimmunology, article-version (VoR) Version of Record, OncoImmunology, Vol 9, Iss 1 (2020)
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- Pancreatic ductal adenocarcinoma (PDAC) is one of the most common tumor subtypes and remains associated with very poor survival. T cell infiltration into tumor tissue is associated with improved clinical outcome but little is known regarding the potential role of NK cells in disease control. Here we analyze the phenotype and function of NK cells in the blood and tumor tissue from patients with PDAC. Peripheral NK cells are present in normal numbers but display a CD16hiCD57hi phenotype with marked downregulation of NKG2D. Importantly, these cells demonstrate reduced cytotoxic activity and low levels of IFN-γ expression but instead produce high levels of intracellular IL-10, an immunoregulatory cytokine found at increased levels in the blood of PDAC patients. In contrast, NK cells are largely excluded from tumor tissue where they display strong downregulation of both CD16 and CD57, a phenotype that was recapitulated in primary NK cells following co-culture with PDAC organoids. Moreover, expression of activatory proteins, including DNAM-1 and NKP30, was markedly suppressed and the DNAM-1 ligand PVR was strongly expressed on tumor cells. As such, in situ and peripheral NK cells display differential features in patients with PDAC and indicate local and systemic mechanisms by which the tumor can evade immune control. These findings offer a number of potential options for NK-based immunotherapy in the management of patients with PDAC.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
Immunology
NK cells
immunomodulation
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Pancreatic cancer
Immunology and Allergy
Medicine
Cytotoxic T cell
Humans
RC254-282
cancer Immunology
Cancer immunology
Original Research
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
PDAC
Immunotherapy
RC581-607
medicine.disease
NKG2D
Interleukin-10
Killer Cells, Natural
Pancreatic Neoplasms
Interleukin 10
030104 developmental biology
Cytokine
Phenotype
Oncology
030220 oncology & carcinogenesis
Cancer research
Immunologic diseases. Allergy
business
Research Article
Carcinoma, Pancreatic Ductal
Subjects
Details
- Language :
- English
- ISSN :
- 2162402X and 21624011
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Oncoimmunology
- Accession number :
- edsair.doi.dedup.....be4e548f70f41670896ae97556d3b71f