The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment

PLoS One. 2016 Jun 8;11(6):e0156497. doi: 10.1371/journal.pone.0156497. eCollection 2016.

Abstract

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).

Conclusion: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / immunology
  • Adenocarcinoma* / mortality
  • Adenocarcinoma* / pathology
  • Adult
  • Antigens, CD / immunology
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Humans
  • Intestinal Neoplasms* / drug therapy
  • Intestinal Neoplasms* / immunology
  • Intestinal Neoplasms* / mortality
  • Intestinal Neoplasms* / pathology
  • Killer Cells, Natural* / immunology
  • Killer Cells, Natural* / pathology
  • Male
  • Natural Killer T-Cells* / immunology
  • Natural Killer T-Cells* / pathology
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / immunology
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Survival Rate

Substances

  • Antigens, CD

Grants and funding

This work was supported by grants from the Swedish Cancer Society [grant number 2014/540 to KJ] (https://www.cancerfonden.se); the Swedish Research Council (http://www.vr.se); the Swedish Government Grant for Clinical Research, the Gunnar Nilsson Cancer Foundation (http://www.cancerstiftelsen.com); the Mrs Berta Kamprad Foundation, Lund University Faculty of Medicine and University Hospital Research Grants (http://www.lu.se). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.