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(1) Background: This study investigates the tumor immune microenvironment, focusing on immune cell distribution in lung adenocarcinoma. (2) Methods: We evaluated fifty cases of lung adenocarcinoma, and suitable areas for further studies were annotated on the histological slides. Two tumor cores per case were obtained, one from the tumor's center and another from its periphery, and introduced into three paraffin receptor blocks for optimized processing efficiency. The 4-micrometer-thick tissue microarray sections were stained for H&E and for CD68, CD163, CD8, CD4, and PD-L1; (3) Results: Our investigation revealed significant correlations between PD-L1 expression in tumor cells and the presence of CD163+ macrophages, between CD4+ cells and CD8+, CD68+, and CD163+ cells, and also between CD8+ T cells and CD163+ cells. Additionally, while we observed some differences in cellular components and densities between the tumor center and periphery, these differences were not statistically significant. However, distinct correlations between PD-L1 and immune cells in these regions were identified, suggesting spatial heterogeneity in the immune landscape. (4) Conclusions: These results emphasize the intricate interactions between immune cells and tumor cells in lung adenocarcinoma. Understanding patient spatial immune profile could improve patient selection for immunotherapy, ensuring that those most likely to benefit are identified. [ABSTRACT FROM AUTHOR]

Background: Survival rates among non-small cell lung cancer (NSCLC) stage IIIA (N2) patients are generally low and depend on the treatment. Patients and methods: We aimed to identify predictive markers for long term survival in responders and non-responders to chemotherapy, analyzing tumour and non-tumour samples by microarray (n=35) and whole exome sequencing (WES, n=25). Results: WES data showed correlation of overall survival of all patients with rs9905892 in the SLFN12L gene. High frequency of mutations (4/6, 66.7%) was identified in members of SWI/SNF complex in responder patients and in patients that were alive after seven years. Microarray data for immune components showed that VISTA (VSIR) was down-regulated in tumoral tissue. Conclusion: Our research suggests that mutations in SWI/SNF complex associate with long term survival after multimodal treatment, while down-regulation of VISTA might indicate its immunomodulatory role in NSCLC stage III (N2) patients. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease., Methods: We describe an integrated whole-exome sequencing and transcriptomic study of 37 iCCAs patients in Germany., Results: We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs., Conclusions: By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)