Prognostic nutritional index and neutrophil-lymphocyte ratio predict toxicities and prognosis in patients with cervical cancer treated with curative radiochemotherapy.

BACKGROUND: This study aimed to investigate the influence of immunonutritional factors on treatment-related toxicities and survival outcomes in patients with cervical cancer undergoing definitive radiochemotherapy. METHODS: Patients with cervical cancer who received curative radiochemotherapy between 2016 and 2021 were retrospectively investigated. Pretreatment prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were measured. Survival outcomes, acute and late toxicities were evaluated. RESULTS: Among the 138 patients, those with larger tumor diameters had significantly lower pre-treatment PNI (p = 0.005). Pre-treatment immunonutritional factors were predictive of clinical survival, whereas post-treatment factors did not correlate with prognosis. Patients with low pre-treatment PNI (<49.5) or high NLR (>2.4) had shorter progression-free survival (PFS, HR: 1.86, p = 0.045 for PNI; HR: 3.15, p = 0.002 for NLR) and overall survival (OS, HR: 1.80, p = 0.048 for PNI; HR: 3.83, p = 0.015 for NLR). High pre-treatment NLR was associated with an increased risk of acute diarrhea (p = 0.049) and late severe toxicities (p = 0.046). Combined analysis revealed that pre-treatment good nutritional status and low systemic inflammation were linked to longer PFS (p = 0.007) and OS (p = 0.002), and poor nutritional status and substantial systemic inflammation were associated with higher rates of late severe toxicities (p = 0.036), with higher prognostic value in advanced stage patients. CONCLUSIONS: Pretreatment immunonutritional measures serve as quantitative biomarkers for predicting survivals and treatment toxicities in patients with cervical cancer treated with definitive radiochemotherapy.

Genotypic Regulation of Type I Interferon Induction Pathways by Frameshift (F) Proteins of Hepatitis C Virus.

Hepatitis C virus (HCV) has evolved mechanisms to evade innate immunity that are leading to chronic infections. The immunological function of the HCV frameshift (F) protein, which is a frameshift product of core coding sequences, has not been well characterized. The HCV F protein is produced during natural HCV infections and is found most commonly in genotype 1 HCV. In this study, we investigated whether the F protein plays a role in type I interferon (IFN) induction pathways. We engineered F expression constructs from core coding sequences of 4 genotypes (1a, 2a, 3a, and 4a) of HCV as well as the sequences which would only be able to produce core proteins. The peptide lengths and amino acids sequences of F proteins are highly variable. We hypothesized that F proteins from different genotypes might control the type I IFN production and response differently. We found that both IFN-beta (IFN-ß) promoter activities are significantly higher in genotype 1a F protein (F1a)-expressing cells. Conversely, the IFN-ß promoter activities are lower in genotype 2a F (F2a) protein-expressing cells. We also used real-time PCR to confirm IFN-ß mRNA expression levels. By generating chimera F proteins, we discovered that the effects of F proteins were determined by the amino acid sequence 40 to 57 of genotype 1a. The regulation of type I IFN induction pathway is related but not limited to the activity of F1a to interact with proteasome subunits and to disturb the proteasome activity. Further molecular mechanisms of how F proteins from different genotypes of HCV control these pathways differently remain to be investigated.IMPORTANCE Although naturally present in HCV infection patient serum, the virological or immunological functions of the HCV F protein, which is a frameshift product of core coding sequences, remain unclear. Here, we report the effects of the HCV F protein between genotypes and discuss a potential explanation for the differential responses to type I IFN-based therapy among patients infected with different genotypes of HCV. Our study provides one step forward to understanding the host response during HCV infection and new insights for the prediction of the outcome of IFN-based therapy in HCV patients.

Placenta-Derived Mesenchymal Stem Cells Reduce the Interleukin-5 Level Experimentally in Children with Asthma.

Background: Mesenchymal stem cells (MSCs) have been investigated as a new treatment option for various diseases in recent years. However, the role of placenta-derived MSCs in children with asthma remains unclear. We assessed the effect of placenta-derived MSCs on T cell immune responses and cytokine IL-5 levels according to cultures in children with and without asthma. Study design: We enrolled children with and without asthma and recorded asthma symptom scores in the asthma group. Blood samples from children were collected to isolate peripheral blood mononuclear cells (PBMCs) and determine the total IgE level. The PBMCs were cultured in vitro with or without MSCs after stimulation with human anti-CD3 and anti-CD28 antibodies (0.5 µg/mL) to evaluate the effect of placenta-derived MSCs. Flow cytometry was performed to detect the activation and proliferation of CD4+ and CD8+ T cells. Pre- and post-culture IL-5 levels were measured in all samples. Results: The percentages of activation and proliferation among CD4+ and CD8+ T cells after coculture with MSCs were significantly lower in the asthma group (P < 0.05). IL-5 levels differed significantly between the PBMC culture and PBMC + MSC (P+S) coculture in the asthma group (P < 0.05). IL-5 levels differed significantly between the PBMC culture and P+S coculture in both the lower (P < 0.05) and higher (P < 0.0005) IgE asthma subgroups. IL-5 levels were also decreased in children with all severities of asthma (P < 0.05). Conclusions: Placenta-derived MSCs exerted an anti-IL-5 effect and reduced the IL-5 level in culture in different subgroups of children with asthma.