Decreased levels of Th17 cells are associated with invasion fungal infections after allogeneic hematopoietic stem cell transplantation

<p><b>Background:</b> Delayed immune reconstitution is an important risk factor for increased susceptibility to fungal pathogens. However, little is known about the association between the recovery of CD4⁺T cell subsets and invasion fungal infections (IFIs) in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to analyze the immune reconstitution characteristics of CD4⁺T cell subsets and their association with the incidence of IFIs over the first 3 months after allo-HSCT.</p> <p><b>Methods</b>: Fifty-three patients were included, 13 with IFIs. We assessed CD4⁺T cell subsets and the mRNA expression of specific transcription factors T-bet, GATA3, RORγt, and Foxp3 in peripheral blood mononuclear cells over three time points. The serum levels of IFN-γ, IL-6, IL-10, and TGF-β were detected using the enzyme-linked immunosorbent assay.</p> <p><b>Results:</b> CD4⁺T cell subsets increased progressively in non-IFI patients after allo-HSCT. In IFI patients, Th17 cell counts were significantly decreased compared to non-IFI patients at 3 months after allo-HSCT. IFI patients showed the lower ratios of RORγt/GATA3 and RORγt/Foxp3 compared with non-IFI patients. In addition, we observed increased levels of IFN-γ and IL-10 in IFI patients after allo-HSCT. In the multivariate analysis, the occurrence of IFIs was independently associated with the incidence of IFIs. Finally, we observed a lower CD4:CD8 ratio in IFI patients and its association with Th17 cells.</p> <p><b>Conclusions:</b> These findings supported that Th17 cells may be involved in the immune pathology of IFIs after allo-HSCT.</p

PD-1 Antibody Monotherapy for Malignant Melanoma: A Systematic Review and Meta-Analysis

<div><p>Antibodies targeting programmed death 1 (PD-1) help prevent tumor cells from escaping immune-mediated destruction. We conducted this systematic review and meta-analysis to gain insight into the efficacy of PD-1 antibodies for the treatment of melanoma. Five trials involving 2,828 adult patients were included in this meta-analysis. In patients with previously untreated or refractory melanoma, treatment with PD-1 antibodies significantly improved the six-month progression-free survival (PFS) (HR 0.55, 95% CI 0.50–0.60, P<0.00001) and the overall response rate (OR 3.89, 95% CI 3.12–4.83, P<0.00001). This meta-analysis indicated that anti-PD-1 treatment might provide a significant survival benefit in patients with melanoma. In addition, we found that patients treated with nivolumab reported significantly fewer treatment-related adverse events (OR 0.74, 95% CI 0.57–0.97, P = 0.03) than those treated with other agents, but there was a dose-dependent increase in the frequency of adverse events in patients treated with pembrolizumab.</p></div

Descriptive summary of the included patients and randomized trials.

<p>Descriptive summary of the included patients and randomized trials.</p

Meta-analysis of the 6-month PFS rates in the PD-1 antibody monotherapy groups and the other groups.

<p>The six-month PFS rate was greater among patients who received PD-1 antibodies than among those who received other treatments.</p

Risk of bias summary.

<p>The overall risk of bias was rated as low in all eligible studies.</p

Flow diagram of the literature search.

<p>Flow diagram of the literature search.</p

Meta-analysis of the overall treatment-related adverse events associated with pembrolizumab.

<p>Subgroup analysis of patients treated with different doses of pembrolizumab revealed a dose-dependent increase in adverse events.</p

Risk of bias graph.

<p>The overall risk of bias was rated as low in all eligible studies.</p

Meta-analysis of the overall treatment-related adverse events associated with nivolumab.

<p>Patients treated with nivolumab had a lower incidence of adverse events.</p

Descriptive summary of treatment-related adverse events.

<p>Descriptive summary of treatment-related adverse events.</p