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

Lundgren, Sebastian; Karnevi, Emelie; Elebro, Jacob; Nodin, Björn; Karlsson, Mikael C. I.; Eberhard, Jakob; Leandersson, Karin; Jirström, Karin

doi:10.1186/s12967-017-1256-y

Cited by 25 publications

(14 citation statements)

References 33 publications

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“…The literature to date on the prognostic significance of MARCO in cancer is sparse. Sun et al (22) reported that a decreased expression of MARCO was associated with tumor progression and poor prognosis in hepatocellular carcinoma and Lundgren et al (23) showed that high density of MARCO + TAMs in certain subtypes of periampullary pancreatic cancer predicted shorter survival. To the best of our knowledge, the expression and prognostic impact of MARCO in GE adenocarcinoma has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

et al. 2020

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Background: Despite improvements in surgical methodologies and perioperative chemo-and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68 + , CD163 + , and MARCO + macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan-Meier analysis, log-rank test, and Cox proportional hazards modeling. Results: Increased infiltration of both CD68 + and CD163 + , but not MARCO + , macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68 + TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163 + TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68 + macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02-2.55, and p = 0.041). Conclusion: Infiltration of CD68 + and CD163 + , but not MARCO + , macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

et al. 2020

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“…Hilly et al [18] reported that higher CD1a + DCs in ltration around the tumor was associated with a higher risk of recurrence in surgically treated cases of early squamous cell carcinoma of the tongue. Lundgren et al [19] reported that a high density of in ltrating CD1a + DCs is an unfavorable prognostic factor in the pancreato-biliary type of periampullary adenocarcinoma. One of the possible reasons for this discrepancy in ndings is the widely varying methods used to evaluate CD1a + DCs in the previous series.…”

Section: Discussionmentioning

confidence: 99%

“…Comprehensive informed consent for the use of resected tissue for research was obtained from all patients, and the study protocol was approved by the Ethics Committee of the Faculty of Medicine at Saga University (No. 2020-04-R- 19).…”

Section: Patientsmentioning

confidence: 99%

Infiltration of CD1a-Positive Dendritic Cells in Advanced Laryngeal Cancer Correlates with Unfavorable Outcomes Post-Laryngectomy

Minesaki

Kai

Kuratomi

et al. 2020

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Background: The prognosis of advanced laryngeal cancer is unfavorable despite the progress of multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer has not been clear.Patients and Methods: We retrospectively analyzed the cases of 57 patients with Stage Ⅲ or Ⅳ laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry for CD1a, S100, and CD8 was performed using representative resected specimens. CD1a+ DCs, S100+ DCs, and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and we divided the cases into high and low groups by the cut-off of the median value for each of these three parameters.Results: Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (p=0.0082) and overall survival (OS) (p=0.0324). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. Multivariate analyses indicated that the infiltration of CD1a+ DCs is an independent unfavorable prognostic factor in both DSS (p=0.0093) and OS (p=0.0132).Conclusions: Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes. It is not yet known why the presence of CD1a+ DCs lead to an unfavorable clinical outcome in laryngeal cancer. Further studies are necessary to validate our results and clarify the function(s) of tumor-infiltrating CD1a+ DCs.

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“…Deficient MMR (dMMR) was defined as negative staining for MLH1, PMS2, MSH2 or MSH6, and proficient MMR (pMMR) was defined as positive staining for all four MMR proteins. Immunohistochemical analysis of CD3 + lymphocytes, CD56 + natural killer (NK)/NKT cells and CD68 + and CD163 + macrophages had been performed previously [ 27 , 28 ]. For immunohistochemical analysis of FoxP3 and CD8 + T cells, 4 μm TMA-sections were automatically pre-treated using the PT Link system and then stained in an Autostainer Plus (Dako; Glostrup, Denmark) with the anti-FoxP3 antibody (clone 236A/E7, mouse, dilution 1:200, Abcam, Cambridge, UK), and the anti-CD8 antibody (clone C8/144B, mouse; dilution, 1:50; product M7103; Dako).…”

Section: Methodsmentioning

confidence: 99%

Relationship between mismatch repair immunophenotype and long-term survival in patients with resected periampullary adenocarcinoma

et al. 2018

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BackgroundPeriampullary adenocarcinomas, including pancreatic cancer, are a heterogeneous group of tumors with poor prognosis, where classification into intestinal type (I-type) or pancreatobiliary type (PB-type) is a relevant prognostic factor. The clinical significance of deficient mismatch repair (dMMR) in periampullary adenocarcinoma is comparatively unexplored. Herein, we examined the associations of MMR immunophenotype with long-term survival in patients with resected periampullary adenocarcinoma, with particular reference to morphology and adjuvant treatment response.MethodsMMR protein expression was assessed by immunohistochemistry on tissue microarrays with primary tumors from a retrospective cohort of 175 patients with periampullary adenocarcinoma treated with pancreaticoduodenectomy during 2001–2011 in Malmö and Lund University Hospitals, Sweden. Cox proportional hazards models were applied to calculate hazard ratios (HR) and 95% confidence intervals (CI).ResultsAfter a mean follow-up of 46.5 (1.9–185.1) months, 35 patients (20.3%) were alive, 24 with I-type and 11 with PB-type tumors. MMR protein expression could be evaluated in 172 cases, in which dMMR was denoted in 20 (11.6%) cases, 13/63 (20.6%) in I-type and 7/109 (6.4%) in PB-type tumors. dMMR was associated with a significantly prolonged overall survival in the entire cohort (HR = 0.28, 95% CI 0.13–0.57), and in I-type tumors (HR = 0.20, 95% CI 0.06–0.68), however not independent of conventional prognostic factors. In PB-type tumors, dMMR was not prognostic, but there was a significant negative interaction between dMMR and adjuvant treatment (pinteraction = 0.015).ConclusionsdMMR is more frequent in I-type compared to PB-type periampullary adenocarcinoma, and is a prognostic factor for long-term survival only in the former. The finding of the small number of PB-type tumors with dMMR potentially lacking benefit from adjuvant chemotherapy is however noteworthy and merits further validation.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1444-4) contains supplementary material, which is available to authorized users.

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

Cited by 25 publications

References 33 publications

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

Infiltration of CD1a-Positive Dendritic Cells in Advanced Laryngeal Cancer Correlates with Unfavorable Outcomes Post-Laryngectomy

Relationship between mismatch repair immunophenotype and long-term survival in patients with resected periampullary adenocarcinoma

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