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High immune cell score predicts improved survival in pancreatic cancer

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Abstract

Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. T-lymphocyte-based immunoscore has proved to be a prognostic factor in colon cancer, but its significance in pancreatic cancer is poorly known. Total of 108 patients operated (R0/R1) for pancreatic ductal adenocarcinoma (PDAC) (TNM stage I–II) were included in the study. Immune cell score (IS) was determined by scoring the samples from grade 0 to 4 according to the number of immune cells (CD3+ and CD8+) in tumor core and invasion margin using tissue microarrays, immunohistochemistry, and digital analysis. Tumors with microsatellite instability were identified by MLH1 immunostaining. High IS and low histological grade were significantly associated with better disease-specific survival (DSS) and overall survival (OS). The 5-year DSS rate for low, moderate, and high IS groups were 5.0, 15.2, and 33.4%, respectively (p = 0.007). The 5-year OS rate for the low, moderate, and high IS groups were 4.2, 13.4, and 31.5%, respectively (p = 0.004). In addition, IS and prognosis varied within a single TNM stage. There was no association between IS and any of the clinicopathological variables. IS was shown to be an independent prognostic factor for better DSS and OS in multivariate analysis, together with the histological grade of the tumor and perineural invasion. Five MLH1-negative tumors (4.6%) were found showing no correlation with IS. IS could be a useful prognostic marker in patients with PDAC treated by primary surgery.

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Abbreviations

IS:

Immune cell score

PDAC:

Pancreatic ductal adenocarcinoma

DSS:

Disease-specific survival

OS:

Overall survival

TMA:

Tissue microarray

MSI:

Microsatellite instability

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Acknowledgements

We thank Marjukka Friman and Teijo Kuopio for their excellent assistance during this study.

Funding

This study received funding from the Finnish Cancer Foundation, Jane and Aatos Erkko Foundation and the State Research Funding.

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Correspondence to Kyösti Tahkola.

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The use of patient samples and the data inquiry were approved by the Oulu University Hospital Ethics Committee. The need to obtain a written or oral consent from the patients for using the samples in research was waived by the Finnish National Authority for Medicolegal Affairs (VALVIRA, Dnro 10832/06.01.03.01/2014).

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The authors declare that they have no conflicts of interest.

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Tahkola, K., Mecklin, JP., Wirta, EV. et al. High immune cell score predicts improved survival in pancreatic cancer. Virchows Arch 472, 653–665 (2018). https://doi.org/10.1007/s00428-018-2297-1

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