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

Sebastian Lundgren, Carl Fredrik Warfvinge, Jacob Elebro, Margareta Heby, Björn Nodin, Agnieszka Krzyzanowska, Anders Bjartell, Karin Leandersson, Jakob Eberhard, Karin Jirström, Sebastian Lundgren, Carl Fredrik Warfvinge, Jacob Elebro, Margareta Heby, Björn Nodin, Agnieszka Krzyzanowska, Anders Bjartell, Karin Leandersson, Jakob Eberhard, Karin Jirström

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Sample immunohistochemical images.
Fig 1. Sample immunohistochemical images.
Immunohistochemical images of CD56 staining in periampullary adenocarcinoma. Sample images (40X magnification) visualising the presence of intra-tumoural (red arrow), stromal (black arrow) and tumour-adjacent (blue arrow) CD56+ NK/NKT cells in three different cases with A) papilla-ampulla intestinal origin, total CD56+ NK/NKT cell count 10, and tumour-specific CD56 expression 0, B) distal bile duct origin, total CD56+ NK/NKT cell count 6 and tumour-specific CD56 expression C) pancreas origin, total CD56+ NK/NKT cell count 5, and tumour-specific CD56 expression 100%.
Fig 2. Kaplan-Meier estimates of survival according…
Fig 2. Kaplan-Meier estimates of survival according to NK/NKT cell density.
Kaplan-Meier estimates of 5-year overall survival according to high and low CD56+ NK/NKT cell count in (A) the entire cohort, (C) in I-type tumours and (E) in PB-type, and recurrence free survival in (B) the entire cohort, (D) in I-type tumours and (F) in PB-type tumours.
Fig 3. Kaplan-Meier estimates of survival according…
Fig 3. Kaplan-Meier estimates of survival according to NK/NKT cell density and adjuvant chemotherapy.
Kaplan–Meier estimates of 5-year overall survival in combined strata according to high and low CD56+ count and adjuvant chemotherapy, respectively, in (A) I-type tumours and (B) PB-type tumours.

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Source: PubMed

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