This study aimed to explore the spatio-temporal expression patterns of congenital anomalies of kidney and urinary tract (CAKUT) candidate genes, Fibroblast Growth Factor Receptor 1 (FGFR1), Fibroblast Growth Factor Receptor 2 (FGFR2) and Receptor-Interacting Protein Kinase 5 (RIP5), in human fetal kidney development (CTRL) and kidneys affected with CAKUT. Human fetal kidneys from the 22nd to 41st developmental week (duplex, hypoplastic, dysplastic, and controls) were stained with antibodies and analyzed by epifluorescence microscopy and RT−qPCR. The effect of CAKUT candidate genes on kidney nephrogenesis and function is confirmed by statistically significant variations in the spatio-temporal expression patterns of the investigated markers. The nuclear localization of FGFR1, elevated expression score of FGFR1 mRNA, the increased area percentage of FGFR1-positive cells in the kidney cortex, and the overall decrease in the expression after the peak at the 27th developmental week in dysplastic kidneys (DYS), suggest an altered expression pattern and protein function in response to CAKUT pathophysiology. The RT−qPCR analysis revealed a significantly higher FGFR2 mRNA expression score in the CAKUT kidneys compared to the CTRL. This increase could be due to the repair mechanism involving the downstream mediator, Extracellular Signal-Regulated Kinase 1/2 (ERK1/2). The expression of RIP5 during normal human kidney development was reduced temporarily, due to urine production and increased later since it undertakes additional functions in the maturation of the postnatal kidney and homeostasis, while the expression dynamics in CAKUT-affected kidneys exhibited a decrease in the percentage of RIP5-positive cells during the investigated developmental period. Our findings highlight the importance of FGFR1, FGFR2, and RIP5 as markers in normal and pathological kidney development.

The aim of this study was to analyse the expression of PD-L1 in non-small cell lung cancer (NSCLC) and its correlation with immune microenvironment response (IMR), clinic-pathological parameters, and outcome. The sample included 76 male and 32 female patients who underwent surgical resection. The mean age of the males was 66 years, and that of the females was 64 years. Adenocarcinoma (ADC) was diagnosed in 68 (63%) cases, squamous cell carcinoma in 35 (32%) cases, and NSCLC (not otherwise specified) in 5 (5%) cases. Metastatic lymph nodes were found in 38 (36%) patients, 18 with N1 nodes and 20 with N2 nodes. PD-L1 expression was valuated as the percentage of positive cancer cells among all cancer cells. Gender, age, and histologic type were not associated with PD-L1 expression (all p > 0.05). The subtypes of ADC were associated with PD-L1 expression (p = 0.050). The papillary subtype was 4.3 times more common among PD-L1 negative than PD-L1 positive ADC; the solid subtype was 1.9 times more common among PD-L1 positive than PD-L1 negative ADC. IMR was predominantly strong in 19 cases, weak in 36, and absent in 53 cases. The median value of PD-L1 expression in cancer cells was positively correlated with IMR (p = 0.039). PD-L1 expression was not correlated with overall survival (p = 0.643). The patients with strong, inflammatory-like IMR had an average survival time that was 12 months longer than patients with absent/low IMR (LR = 2.8; p = 0.132). In conclusion, the papillary subtype was more commonly PD-L1 negative in comparison with other subtypes of ADC. Positive PD-L1 expression in tumour cells was connected with strong, inflammatory-like IMR. Patients with strong IMR tended to experience better outcomes. Further investigations are needed on larger-scale cohorts to elucidate the insights of this descriptive study.

Background and Objectives: This study explores the immunological landscapes of non-melanoma skin neoplasms (NMSNs), specifically keratoacanthoma (KA), squamous cell carcinoma (SCC), and common warts (VV). Although benign, KA shares histological similarities with low-grade SCC. The tumor microenvironment (TME) plays a key role in tumor progression, affecting angiogenesis, inflammation, and immune evasion. Viral infections, particularly human papillomavirus (HPV), are linked to NMSN development, with various HPV types identified in KA. VV, caused by HPV, serves as a comparative model due to its similar etiopathogenesis. Materials and Methods: This research examines the expression of CTLA4, a critical regulator of T-cell homeostasis, and IFN-γ, a cytokine with immunomodulatory and antiviral effects, in the TME of 41 KA, 37 SCC, and 55 VV samples using multichannel immunofluorescence. Results: The analysis revealed distinct patterns of CTLA4 and IFN-γ expression. SCC exhibited a higher prevalence of CTLA4+IFN-γ+ double-positive lymphocytes, suggesting a more immunosuppressive TME. In contrast, VV showed the highest expression of CTLA4+ cells, while both KA and VV had lower expressions of IFN-γ+ lymphocytes compared to SCC. The increased presence of CTLA4+IFN-γ+ double-positive lymphocytes in SCC suggests that the co-expression of these markers may exert a stronger effect on TME modulation than CTLA4 alone. Conclusions: These findings underscore the potential of immune profiling as a diagnostic tool to differentiate between benign and malignant lesions, such as KA and SCC. Furthermore, the presence of CTLA4+IFN-γ+ lymphocytes, particularly in SCC, may serve as a biomarker for tumor progression and a potential target for future immunotherapy strategies aimed at modulating the immune response in NMSN.