Abstract
BackgroundDendritic 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.MethodsThe 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).ResultsHigh 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.ConclusionsThe 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.
Highlights
Dendritic cells (DC) and tumour-associated macrophages (TAM) are essential in linking the innate and adaptive immune response against tumour cells and tumour progression
The findings of the present study indicate that it is this study demonstrated an association between high density of CD68+ and CD163+ TAMs with poor prognosis in the whole cohort, but not in strata according to morphological type, and not independent of established clinical prognostic factors
The present study found a significant association between macrophage receptor with collagenous structure (MARCO)+ cells and CD68+ cells which confirms the results of Sun et al, where MARCO+ cells co-localized with CD68+ macrophages [31]
Summary
Dendritic cells (DC) and tumour-associated macrophages (TAM) are essential in linking the innate and adaptive immune response against tumour cells and tumour progression. 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. 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. Periampullary adenocarcinoma, including pancreatic cancer, is a heterogenous group of tumours that originate in the area around the caput pancreatitis and the periampullary region They have a dismal prognosis due to lack of symptomatology until late stages and lack of effective conventional therapy. TAMs, both C D68+ and CD163+, located in the stromal compartment have been shown to have prognostic value in breast cancer, illustrating that the localisation of TAMs within the histological architecture is relevant [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
