Comment on 'Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area'

We comment on the recent study by Sideras et al (2015) that combines tissue microarrays (TMAs) and immunohistochemistry to investigate the expression pattern of 15 antigens belonging to different categories, including cancer-testis antigens and oncofetal proteins in hepatocellular carcinoma (HCC). Because current therapies for HCC are far from ideal (Ilan, 2014) and immunotherapy has been suggested as a potential therapeutic option, the Authors aimed at identifying a panel of biologically relevant tumour antigens with broad expression in a western European population of HCC patients and specific expression in the tumour tissue with no, or little, expression in surrounding non- tumoral tissue (Sideras et al., 2015)

Fusobacterium nucleatum and the Immune System in Colorectal Cancer

The current literature suggests that Fusobacterium nucleatum, a Gram-negative oral anaerobe, may significantly contribute to CRC development. Furthermore, the presence of Fusobacterium nucleatum in CRCs has also been associated with MSI-high status, lower levels of infiltrating T-lymphocytes, and poor clinical outcomes. We believe that the integration of new technologies, including genomics, bioinformatics and systems medicine, may help to better understand how Fusobacterium nucleatum, immunity status, and environmental factors interact in the initiation and progression of CRCs and generate further information regarding prognostic and therapeutics options for this tumor

Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

PURPOSE: Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients. MATERIALS AND METHODS: All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F\u2009=\u200942:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months. RESULTS: Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p\u2009=\u20090.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84-14.01 %), CD8-TILs of 2.9 % (range: 0.11-11.92 %), PD-1 of 0.65 % (range: 0.02-5.87 %), and PD-L1 of 0.7 % (range: 0.03-10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho\u2009=\u20090.31; p\u2009=\u20090.027) and PD-1 (rho\u2009=\u20090.33; p\u2009=\u20090.017 and rho\u2009=\u20090.36; p\u2009=\u20090.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho\u2009=\u20090.45; p\u2009=\u20090.001), CD8 TILs and PD-L1 (rho\u2009=\u20090.41; p\u2009=\u20090.003), CD68-TAMs and PD-L1 (rho\u2009=\u20090.30; p\u2009=\u20090.027), PD-1 and PD-L1 (rho\u2009=\u20090.26; p\u2009=\u20090.059). With respect to patients' outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p\u2009=\u20090.002, 0.004, and <0.001, respectively). CONCLUSIONS: The present study shows a direct association between metabolic parameters on FDG-PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors

Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis: A pilot study

Background: A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. Methods: A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. Results: We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. Conclusion: These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies