ABSTRACT
Objective:To observe the baseline characteristics and clinical efficacy in cancer patients who were treated with immune checkpoint inhibitors (ICIs) and experienced immune-related adverse events (irAEs).Methods:The clinical efficacy in cancer patients experiencing irAEs was retrospectively analyzed, and the objective response rate, progression-free survival, and overall survival were evaluated.Results:The median onset time of irAEs in 23 patients was 3.17 months. There were 47.8% (11/23) patients with multi-system irAEs, 63.3% (7/11) of which were non-simultaneous. The most common irAEs were immune-related pneumonia, hypothyroidism and immune-related liver dysfunction. Complete remission, partial remission and stable disease were respectively achieved in 0, 10 and 11 cases, while the other two patients developed progressive disease. The objective response rate was 43.5% and the disease control rate was 91.3%. With a median follow-up period of 16.5 months, 17 patients (73.9%) had progressive disease and the median progression-free survival was 9.63 months. Eight patients (34.8%) died before reaching the median overall survival. The progression-free survival and overall survival of patients with irAEs ≥grade 3 were significantly shorter than those with irAEs of grade 1-2 ( P<0.01). Conclusions:The occurrence of irAEs might correlate with the short-term efficacy and clinical benefits in patients treated with ICIs.
ABSTRACT
Objective: To investigate the effects of thrombopoietin (TPO) on proliferation and collagen synthesis in pulmonary fibro-blasts induced by TGFβ1. Methods: Cultured human embryonic lung fibroblasts (HFLs) were treated with recombinant human TGF-β1 to induce myofibroblast differentiation. Different concentrations of recombinant human TPO were applied individually or in combina-tion. Cell proliferation rate was determined using the CCK8 assay. Q-PCR and immunofluorescence assay were employed to examine the mRNA and protein expression of α-smooth muscle actin (αSMA) and type I collagen (COL1)A2. Results: TGFβ1 treatment induced HFL transdifferentiation to myofibroblasts was determined by the expression of αSMA, a myofibroblast-specific marker. Cell prolifera-tion increased during the induction. COL1 gene and protein expression were upregulated by TGFβ1 induction (P<0.05). The TGFβ1-in-duced mRNA and protein expression of αSMA and COL1A2 was decreased by TPO treatment (P<0.05), as determined by reverse tran-scription quantitative polymerase chain reaction and immunofluorescence analysis, respectively. The inhibitory rate showed a dose de-pendent effect within a certain TPO concentration range. The CCK8 assay demonstrated that TPO downregulated the TGFβ1-induced proliferation (P<0.05). Furthermore, the expression of heme oxygenase-1 (HO-1) was downregulated in TGFβ1-induced lung fibro-blasts, and these effects were attenuated by TPO administration (P<0.05). Conclusions: TPO can inhibit the TGFβ1-induced prolifera-tion and differentiation of human lung fibroblasts. These effects may be mediated in part by HO-1-related signaling pathways.