Characterization of natural killer and cytotoxic T-cell immune infiltrates in pancreatic ductal adenocarcinoma Journal Article
| Authors: | Persky, J.; Cruz, S. M.; Darrow, M. A.; Judge, S. J.; Li, Y.; Bold, R. J.; Karnezis, A. N.; Matsukuma, K. E.; Qi, L.; Canter, R. J. |
| Article Title: | Characterization of natural killer and cytotoxic T-cell immune infiltrates in pancreatic ductal adenocarcinoma |
| 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. 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). 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. 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. © 2024 Wiley Periodicals LLC. |
| Keywords: | immunohistochemistry; cancer survival; human tissue; protein expression; treatment outcome; aged; human cell; major clinical study; overall survival; pancreatic neoplasms; lymph node metastasis; cancer grading; pancreaticoduodenectomy; adenocarcinoma; cd3 antigen; cd8 antigen; cd8+ t lymphocyte; tumor associated leukocyte; cd8-positive t-lymphocytes; lymphocytes, tumor-infiltrating; metabolism; cell infiltration; carcinoma, pancreatic ductal; cohort analysis; pathology; retrospective study; histology; pancreas tumor; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; cancer size; pancreatectomy; natural killer cell; killer cells, natural; pancreatic cancer; cd3+ t lymphocyte; major histocompatibility antigen class 1; recurrence free survival; cd45ro antigen; clinical outcome; pancreatic ductal carcinoma; cancer prognosis; humans; prognosis; human; male; female; article; natural cytotoxicity triggering receptor 1; date of death; immune infiltrates |
| Journal Title: | Journal of Surgical Oncology |
| Volume: | 129 |
| Issue: | 5 |
| ISSN: | 0022-4790 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2024-04-01 |
| Start Page: | 885 |
| End Page: | 892 |
| Language: | English |
| DOI: | 10.1002/jso.27581 |
| PUBMED: | 38196111 |
| PROVIDER: | scopus |
| PMCID: | PMC10980567 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
