HDAC activity is essential for maintaining the self-renewal and pluripotency of MSCs.

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Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 have shifted the treatment paradigm of advanced non-small cell lung cancer (NSCLC), but responses are often heterogeneous and temporary. Several landmark publications have confirmed the dominant role of gut microbiome in modulating tumor responses to ICIs, suggesting the predictive value of antibiotics (ATB) in patients treated with anti-PD-(L)1 antibody. However, more evidence is needed to comprehensively reveal the association between ATB usage and ICIs therapeutic response in NSCLC, especially in Chinese populations. Method: We retrospectively reviewed the medical records of patients with advanced/metastatic NSCLC received anti-PD-(L)1 based therapies at our hospital. Detailed clinicopathologic characteristics, response data and ATB usage were collected for all patients. The patients receiving ATB within one month around the first administration of ICIs (defined as ATB-treated) were compared to those without (ATB-untreated). Result: 109 cases receiving anti-PD-(L)1 based therapies and underwent response evaluation were identified. 65 (59.3%) of them received monotherapy and 44 received combination therapies including anti-PD-(L)1 plus anti-angiogenesis/chemotherapy. 35 (32.1%) patients had been prescribed ATB 60 days before or during the course of ICIs treatment, and 20 (18.3%) were categorized as ATB-treated group. The most commonly administered ATB were b-lactam inhibitors, fluoroquinolones and macrolides. No major statistical differences in baseline clinicopathologic features were observed between ATB-treated and -untreated groups. The objective response rates (ORR) to ICIs in two groups were 65% and 82%, respectively. ATB treatment was significantly associated with shorter progression-free survival (PFS) (median 3.73 vs 9.3 m, p<0.001), and also tended to be associated with primary disease progression (35% vs 18%, p¼0.087). The overall survival (OS) (median 31.9 vs 37.6 m, p¼0.74) was similar in two groups, but ATB appeared to be related to decreased duration of survival from ICI treatment start to death (median 6.07 vs 26.9 m, p¼0.002). In multivariable analysis, ATB treatment was markedly associated with poorer ORR and survival to ICIs after adjusting for prior line treatment setting, ICI regimens, numbers of ICI-related toxicity and clinical characteristics. Conclusion: ATB usage was a predictor for decreased clinical benefit from anti-PD-(L)1immunotherapies in Chinese NSCLC patients. More comprehensive understanding of the interaction between gut microbiome and ATB is still in urgent need. Furthermore, modulating ATB-related gut microbiome dysbiosis may enhance response to anti-PD-(L)1 immunotherapies.Background: The phase III trials of nivolumab, pembrolizumab or atezolizumab in comparison to standard chemotherapy for advanced non-small cell lung cancer (NSCLC) included a small number of patients with brain metastases. The aim of this study was to evaluate the radiological features of brain metastases after treatment with radiotherapy (...

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Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a severe genodermatosis caused by mutations in COL7A1 and characterized by mucocutaneous blistering after minor trauma. Bone marrowemesenchymal stromal cells (MSCs) have shown therapeutic potential for RDEB patients. Recent preclinical study demonstrated that a systemic infusion of human umbilical cord blood (UCB)-derived nonhematopoietic stem cells correct RDEB murine model. In this study, we wanted to determine the safety and possible clinical efficacy of systemic allogeneic UCB-MSCs therapy for RDEB patients. Six Korean RDEB patients (4 adults and 2 children) were included in this clinical trial. Each participant received three intravenous infusions of allogeneic UCB-MSCs (1e3Â 10 6 cells/kg) with no HLA matching. Change in mean disease severity measured by Birmingham Epidermolysis Bullosa Severity Score (BEBSS) was-16 point at 60 days. Mean BEBSS total body surface area (%) was significantly reduced (-15 point) from baseline to day 60. Blister count and blister area/body surface area (%) were reduced by 50% at day 60 compared to baseline. Pain and pruritus score (VAS) were also reduced by 43% and 13% at day 60 compared to baseline. We also found the increased number of c-kit+ mast cells and CD68+ macrophages in the patient's skin at baseline, but the number of both cells were markedly reduced at day 60. No significant increase in C7 deposition was observed at day 60. There were no severe adverse events during day 180. The results suggest that administration of allogeneic UCB-MSCs in patients with RDEB is safe and provide indications of possible clinical benefits, to be confirmed in further clinical trials.

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