ABSTRACT
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer (NSCLC), is poorly differentiated and highly aggressive. Treatment is limited, and the prognosis is poor. Pembrolizumab is an anti-programmed death (PD)-1 antibody with good efficacy in NSCLC. Recent studies have demonstrated that PD-ligand 1 (PD-L1) overexpression is common in PSCs, which suggests that anti-PD-L1 treatment is an ideal option. However, the response to pembrolizumab in PSC has not been studied. CASE SUMMARY: We present a PSC case with PD-L1 overexpression that significantly benefited from pembrolizumab. A 73-year-old Chinese male was detected with a right lung lesion. Pathological analysis of the right upper lobectomy confirmed PSC. The PD-L1 test revealed overexpression (TPS: 90%). Multiple metastases occurred 1 mo after surgery, representing stage IV PSC. Neither first-line chemotherapy nor second-line antiangiogenic agents showed any benefit. Radiotherapy (1200 cGy) was administered to relieve chest wall pain. The patient received the PD-1 inhibitor pembrolizumab (100 mg) as third-line therapy; however, because of fever and severe infection, he refused to receive immunotherapy any longer. Thus, only one dose of pembrolizumab was administered. Deep sustained remission of most of the metastases was achieved except for lesions in the right adrenal gland, which first shrank and then progressed. The patient died because of disease progression in the right adrenal gland. He achieved a progression-free survival time of 8 mo and an overall survival time of 9 mo with third-line pembrolizumab. CONCLUSION: Our findings highlight and offer direct evidence of the efficacy of pembrolizumab in PD-L1-overexpressing PSCs. Combined radiotherapy and immunotherapy may enhance treatment efficacy.
ABSTRACT
Regulatory T cells (Tregs) play an essential role during homeostasis and tolerance of the immune system. Based on our previous study that exposure of pregnant rats to staphylococcal enterotoxin B (SEB) can alter the percentage of CD4/CD8 subsets in the thymus of the offspring, in this study, we focus on the influence of exposure of pregnant rats to SEB on number, function and response of Tregs in the thymus of the offspring. Pregnant rats at gestational day of 16 were intravenously injected with 15 µg SEB and the thymuses of the neonatal and adult offspring were harvested for this study. We found that exposure of pregnant rats to SEB could significantly increase the absolute number of Tregs and the FoxP3 expression level in the thymus of not only neonatal but also adult offspring. Re-exposure of adult offspring to SEB remarkably reduced the suppressive capacity of Tregs to CD4+ T cells and the expression levels of TGF-ß and IL-10 in the thymus, but had no effect on production of IL-4 and IFN-γ. Furthermore, it also notedly decreased the absolute number of Tregs and the FoxP3 expression level. These data suggest that prenatal exposure of pregnant rats to SEB attenuates the response of increased Tregs to re-exposure to SEB in the thymus of adult offspring.
Subject(s)
Enterotoxins , T-Lymphocytes, Regulatory , Animals , Female , Immune Tolerance , Pregnancy , RatsABSTRACT
OBJECTIVE: To evaluate the methods of reconstruction of laryngeal function after the extended laryngectomy. METHODS: The laryngeal functions were reconstructed after the extended laryngectomy performed on 22 cases with the laryngocarcinoma of T2 and T3 stages of glottic type, using epiglottis and cervical anterior muscle to reconstruct the laryngeal cavity and larynx bracket, from September 1998 to October 1999. RESULTS: Twenty cases recovered normal swallow function in 20 days post-operation as well as the entire function of larynx was recovered, and the rate of decannulation was 90.9% (20/22). One case with pharyngeal fistula recovered a month later, but the other case recovered to normal diet by operation repaired. All the patients pronounced clearly and were able to keep the characteristics of their own voice. The fibred laryngoscope examination showed that the sphincter valves were formed at the larynx atrium in all postoperative cases. The rate of 3-year survival for T2 and T3 stages was 100% (9/9) and 92.3% (12/13), respectively. CONCLUSION: The laryngeal cavity could be enlarged and the laryngeal atrium was reconstructed by employing epiglottis ifraplacement and cervical anterior muscle to reduce the tension of epiglottis and minimize the injury of the membrane as well as to overcome the shortcomings of insufficient material if mere employing epiglottis. The application of combined methods to reconstruct the laryngeal cavity is a practical way to restore the larynx function and improve the life quality.
