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Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy ( P <0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy ( P =0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS ( P <0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy ( OR =0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent ( OR =0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis ( OR =0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy ( HR =0.480, 95% CI: 0.303-0.759). Sex ( HR =0.399, 95% CI: 0.161-0.991, P =0.048), age ( HR =0.356, 95% CI: 0.170-0.745, P =0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

Objective: To investigate the effects of mifepristone (MIF) on the growth of breast cancer., Methods: Forty female athymic BALB/c-nude mice underwent subcutaneous injection of breast cancer cells of the line MCF-7, ER +/PR +. Ten days later when tumor nodules were formed, the mice were randomly divided into 4 equal groups to be administered with MIF of the concentrations of 25 mg, 50 mg, 100 mg, and 200 mg/kg x d respectively by gastric perfusion. The tumor size was observed every 3 day till 3 weeks later. Ten mice were used as normal control group, undergoing gastric perfusion of vegetable oil. Parts of the animals were killed 2 weeks later, and the remaining mice were all killed 3 weeks later. The tumors were taken out and underwent immunochemistry to measure the protein expression of CD34, estrogen receptor (ER), progesterone receptor (PR), vascular endothelial growth factor (VEGF), bcl-2, Ki67, p53, and CerbB-2. Microscopy was used to measure the microvessel density (MVD)., Results: The growth velocity of tumor of the mice of MIF groups were all slower than that of the control group (all P <0.01). The MVD levels of the MIF groups all decreased time- and dose-dependently. Microscopy showed that in the tumor tissues heteromorphism was significant, pathological caryomitosis was more remarkable, karyoplasmic ratio was greater, endochylema was deep blue, mesenchyma was sparse, and zone of neoplasm necrosis became lager in comparison with the control group. The expression levels of VEGF, bcl-2, Ki67, p53, and CerbB-2 of the MIF groups were all significantly lower, time and dose-dependently, than those of the control group (all P <0.05)., Conclusion: MIF inhibits the growth of breast cancer by the mechanisms related to apoptosis promotion and inhibition of angiogenesis, so it can be used in breast cancer endocrine therapy.