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Characterization of natural killer and cytotoxic T-cell immune infiltrates in pancreatic ductal adenocarcinoma.

Authors :
Persky J
Cruz SM
Darrow MA
Judge SJ
Li Y
Bold RJ
Karnezis AN
Matsukuma KE
Qi L
Canter RJ
Source :
Journal of surgical oncology [J Surg Oncol] 2024 Apr; Vol. 129 (5), pp. 885-892. Date of Electronic Publication: 2024 Jan 09.
Publication Year :
2024

Abstract

Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor response to systemic therapies, including immunotherapy. Given the immunotherapeutic potential of natural killer (NK) cells, we evaluated intratumoral NK cell infiltrates along with cytotoxic T cells in PDAC to determine their association with patient outcomes.<br />Methods: We analyzed tumors from 93 PDAC patients treated from 2012 to 2020. Predictor variables included tumor-infiltrating lymphocytes (TILs), T-cell markers (CD3, CD8, CD45RO), NK marker (NKp46), and NK inhibitory marker (major histocompatibility complex class I [MHC-I]) by immunohistochemistry. Primary outcome variables were recurrence-free survival (RFS) and overall survival (OS).<br />Results: Mean TILs, CD3, and NKp46 scores were 1.3 ± 0.63, 20.6 ± 17.5, and 3.1 ± 3.9, respectively. Higher expression of CD3 and CD8 was associated with higher OS, whereas NK cell infiltration was not associated with either RFS or OS. There was a tight positive correlation between MHC-I expression and all T-cell markers, but not with NKp46.<br />Conclusions: Overall NK cell infiltrates were low in PDAC and did not predict clinical outcomes, whereas T-cell infiltrates did. Further characterization of the immune infiltrate in PDAC, including inhibitory signals and suppressive cell types, may yield better biomarkers of prognosis and immune targeting in this refractory disease.<br /> (© 2024 Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1096-9098
Volume :
129
Issue :
5
Database :
MEDLINE
Journal :
Journal of surgical oncology
Publication Type :
Academic Journal
Accession number :
38196111
Full Text :
https://doi.org/10.1002/jso.27581