The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment.
BACKGROUND
Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described.


METHODS
Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS).


RESULTS
High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29-0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014).


CONCLUSIONS
This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers.
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, 221 85, Lund, Sweden.
Sebastian
http://orcid.org/0000-0001-5135-558X
S
Lundgren
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, 221 85, Lund, Sweden.
Carl Fredrik
CF
Warfvinge
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, 221 85, Lund, Sweden.
Jacob
J
Elebro
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, 221 85, Lund, Sweden.
Margareta
M
Heby
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, 221 85, Lund, Sweden.
Björn
B
Nodin
Center for Molecular Pathology, Department of Translational Medicine, Lund University, Lund, Sweden.
Agnieszka
A
Krzyzanowska
Center for Molecular Pathology, Department of Translational Medicine, Lund University, Lund, Sweden.
Anders
A
Bjartell
Center for Molecular Pathology, Department of Translational Medicine, Lund University, Lund, Sweden.
Karin
K
Leandersson
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, 221 85, Lund, Sweden.
Jakob
J
Eberhard
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, 221 85, Lund, Sweden.
Karin
K
Jirström
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
D015703:Antigens, CD