HLA-G is the checkpoint molecule involved in the suppression of the immune response. Increased expression of HLA-G and its ILTs receptors have been correlated with tumor progression in various cancer types. In head and neck squamous cell carcinoma (HNSCC) tumors, the effect of HLA-G, ILT2 and ILT4 expression on cancer development has to be explained. The 34 HNSCC patients and 98 controls were genotyped for the HLA-G 14 bp ins/del polymorphism. In HNSCC lesions, HLA-G, ILT2 and ILT4 mRNA expression was analysed using real-time PCR. The association between HLA-G, ILT2 and ILT4 mRNA expression and clinical variables (age at onset, TNM staging system and p16 positivity) was also evaluated. No genetic association between the HLA-G 14 bp ins/del and HNSCC risk was detected (p > 0.05). However, in the non-metastatic HNSCC group, a significantly higher HLA-G mRNA expression was noted in tumors in the T4 stage compared to those in the T1 and T2 stages (p = 0.0289). ILT2 mRNA expression was significantly increased in non-metastatic vs. metastatic tumors (p = 0.0269). Furthermore, a significantly higher ILT4 mRNA expression was noted in tumors in the T1+T2 stage compared to those in the T3 stage (p = 0.0495). Our results suggest that the HLA-G molecule creates an immunological microenvironment involved in HNSCC development.

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterised by progressive loss of memory. In the AD brain, matrix metalloproteinases (MMPs) are involved in the disruption of the blood-brain barrier resulting in a neuroinflammatory response. The objective of our investigation was to assess the association of MMP2 rs243866 and rs2285053 polymorphisms with susceptibility to AD, to assess the interaction of MMP2 variants with APOE ε4 risk allele, and to evaluate their influence on the age at disease onset and MoCA score. A total of 215 late-onset AD patients and 373 control subjects from Slovakia were genotyped for MMP2 rs243866 and rs2285053 polymorphisms. The MMP2 association with AD risk and clinical parameters was evaluated by logistic and linear regression analyses. No statistically significant differences in either MMP2 rs243866 and rs2285053 allele or genotype frequencies between AD patients and the control group have been observed (p > 0.05). However, the correlation with clinical findings revealed a higher age at disease onset in MMP2 rs243866 GG carriers in the dominant model as compared to other MMP2 genotype carriers (p = 0.024). Our results suggest that MMP2 rs243866 promoter polymorphism may have an impact on the age at AD onset in the patients.

Background: Human leukocyte antigen G (HLA-G) is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities. It belongs to class I non-classical major histocompatibility complex molecules and has been upregulated in various cancer types. In bladder cancer (BC) tumors, the association of HLA-G with cancer progression has to be explained. Methods: A total of 89 BC patients and 74 control subjects were genotyped for the HLA-G 14 bp ins/del polymorphism. In urine cell samples, HLA-G mRNA expression was analyzed using real-time PCR. Soluble HLA-G (sHLA-G) serum levels were measured by ELISA. The associations between the HLA-G 14 bp ins/del polymorphism, HLA-G mRNA expression, and/or sHLA-G levels and selected variables including tumor grade, disease stage, body mass index, and heart rate variability (HRV) parameters were evaluated. Results: The protective HLA-G 14 bp ins/ins genotype under the recessive genetic model was associated with lower HLA-G mRNA expression in the BC group (p = 0.049). Significantly higher HLA-G mRNA expression was detected in patients with pT2 + pT3 as compared to those with pTa + pT1 stages (p = 0.0436). Furthermore, higher HLA-G mRNA expression was observed in high-grade muscle-infiltrating BC (MIBC) than in the low-grade non-MIBC group (p = 0.0365). Patients with a level of sHLA-G above 29 U/mL had shorter disease-free survival than patients with lower sHLA-G levels. Furthermore, the opposite HRV correlations with sHLA-G levels in BC patients as compared to controls probably reflect the different roles of HLA-G in health and cancer. Conclusions: Our results suggest the impact of the HLA-G 14 bp ins/del variant, HLA-G expression, and autonomic nervous system imbalance on advanced stages of BC.

Chronic inflammation contributes to bladder cancer (BC) development and progression through dysregulated cytokine signaling and tumor–immune interactions. This case–control study investigated associations between IL6 rs1800795, TNF rs1800629, CCL2 rs1024611, and VEGFA rs699947 polymorphisms, circulating cytokine levels, clinicopathological characteristics, and autonomic nervous system balance assessed by heart rate variability (HRV) in 73 BC patients and 88 controls. Genotyping was performed using PCR–RFLP, serum cytokine levels were measured by ELISA, and associations were evaluated using logistic, linear regression, and survival analyses. No significant associations with BC risk were observed for IL6, TNF, or VEGFA variants. However, the CCL2 rs1024611 GG genotype was associated with increased BC risk (recessive model: OR = 5.82, p = 0.026). Stratified analyses showed a lower frequency of the IL6 rs1800795 C allele and TNF rs1800629 GA genotype in high-grade and muscle-invasive tumors, suggesting potential associations with reduced tumor aggressiveness. No polymorphism was associated with serum cytokine levels or disease-free survival. In BC patients, the TNF rs1800629 A allele was associated with higher parasympathetic-related HRV indices and lower sympathetic parameters, whereas no such associations were observed in controls. These findings indicate that genetic variation within inflammatory pathways may contribute to BC susceptibility and tumor phenotype and may also modulate neuroimmune interactions.