The clinical importance of tumour-infiltrating macrophages and dendritic cells in periampullary adenocarcinoma differs by morphological subtype

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Lundgren, SebastianLund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups (author)

The clinical importance of tumour-infiltrating macrophages and dendritic cells in periampullary adenocarcinoma differs by morphological subtype

Article/chapterEnglish2017

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2017-07-03
Springer Science and Business Media LLC,2017

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LIBRIS-ID:oai:lup.lub.lu.se:7d4eeef6-5d4d-4877-8fb6-1b1099c0b9d2
https://lup.lub.lu.se/record/7d4eeef6-5d4d-4877-8fb6-1b1099c0b9d2URI
https://doi.org/10.1186/s12967-017-1256-yDOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:136267939URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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Background: Dendritic cells (DC) and tumour-associated macrophages (TAM) are essential in linking the innate and adaptive immune response against tumour cells and tumour progression. These cells are also potential target for immunotherapy as well as providing a handle to investigate immune status in the tumour microenvironment. The aim of the present study was to examine their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, with particular reference to morphological subtype. Methods: The density of tolerogenic immature CD1a+ dendritic cells (DC), and MARCO+, CD68+ and CD163+ tissue-associated macrophages (TAM) was analysed by immunohistochemistry in tissue micro arrays with tumours from 175 consecutive cases of periampullary adenocarcinoma who had undergone pancreaticoduodenectomy, 110 with pancreatobiliary type (PB-type) and 65 with intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analyses were applied to determine the impact of immune cell infiltration on 5-year overall survival (OS). Results: High density of CD1a+ DCs was an independent prognostic factor for a reduced OS in PB-type but not in I-type tumours (adjusted HR = 2.35; 95% CI 1.13-4.87). High density of CD68+ and CD163+ TAM was significantly associated with poor OS in the whole cohort, however only in unadjusted analysis (HR = 1.67; 95% CI 1.06-2.63, and HR = 1.84; 95% CI 1.09-3.09, respectively) and not in strata according to morphological subtype. High density of MARCO+ macrophages was significantly associated with poor prognosis in I-type but not in PB-type tumours (HR = 2.14 95% CI 1.03-4.44), and this association was only evident in patients treated with adjuvant chemotherapy. The prognostic value of the other investigated immune cells did not differ significantly in strata according to adjuvant chemotherapy. Conclusions: The results from this study demonstrate that high infiltration of tolerogenic immature DCs independently predicts a shorter survival in patients with PB-type periampullary adenocarcinoma, and that high density of the MARCO+ subtype of TAMs predicts a shorter survival in patients with I-type tumours. These results emphasise the importance of taking morphological subtype into account in biomarker studies related to periampullary cancer, and indicate that therapies targeting dendritic cells may be of value in the treatment of PB-type tumours, which are associated with the worst prognosis.

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Karnevi, EmelieLund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups(Swepub:lu)med-ekn (author)
Elebro, JacobLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-jce (author)
Nodin, BjörnLund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups(Swepub:lu)immu-bnn (author)
Karlsson, Mikael C.I.Karolinska Institutet,Karolinska Institute (author)
Eberhard, JakobLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)kir-jeb (author)
Leandersson, KarinLund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,Cancer Immunology, Malmö,Lund University Research Groups(Swepub:lu)immu-kpe (author)
Jirström, KarinLund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups(Swepub:lu)pat-kji (author)
Personlig patologi och cancerbehandlingForskargrupper vid Lunds universitet (creator_code:org_t)

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