MicroRNA-326 negatively regulates CD155 expression in lung adenocarcinoma.

Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer. Comprehensive miRNA screening with target prediction programs and a dual-luciferase reporter assay identified miR-346, miR-328-3p, miR-326, and miR-330-5p as miRNAs that bind to the 3'-UTR of CD155 mRNA. Forced expression of these miRNAs suppressed CD155 expression in lung cancer cell lines. Immunohistochemical staining of CD155 in tissue specimens from 57 patients with lung adenocarcinoma revealed the median tumor proportion score for CD155 to be 68%. The abundance of miR-326 in these specimens with a low level of CD155 expression was significantly greater than in specimens with a high level (p < 0.005). Our results thus suggest that miR-326 negatively regulates CD155 expression in lung adenocarcinoma and might therefore play a role in the development of resistance to PD-1/PD-L1 inhibitors.

Regulation of PD-L1 expression in non-small cell lung cancer by interleukin-1ß.

Introduction: Programmed cell death-ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1ß (IL-1ß) plays a key role in regulation of PD-L1 expression in non-small cell lung cancer (NSCLC). Methods: We performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1ß in vitro to elucidate its induction of PD-L1 on NSCLC cells. Results: The IL-1ß gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1ß and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1ß and IFN-γ also cooperatively activated mitogen-activated protein kinase (MAPK) signaling and promoted the binding of downstream transcription factors to the PD-L1 gene promoter. Furthermore, inhibitors of MAPK signaling blocked upregulation of PD-L1 by IL-1ß and IFN-γ. Discussion: Our study reports high levels of IL-1ß in the tumor microenvironment may cooperate with IFN-γ to induce maximal PD-L1 expression in tumor cells via activation of MAPK signaling, with the IL-1ß-MAPK axis being a promising therapeutic target for attenuation of PD-L1-mediated suppression of antitumor immunity.

Pleuroparenchymal fibroelastosis secondary to autologous peripheral blood stem cell transplantation: A case report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonitis. Although most cases of PPFE are idiopathic, some cases of PPFE occur secondary to stem cell transplantation. We report a 41-year-old woman developed pneumonia after autologous peripheral blood system cell transplantation (PBSCT). Eleven years after PBSCT, she presented with dyspnea. A computed tomographic scan showed pleuroparenchymal thickening and predominantly in the upper lobes. She was diagnosed with PPFE secondary to PBSCT. She was started nintedanib and administered oxygen therapy. Most cases of PPFE secondary to stem cell transplantation have been reported. However, we experienced the case of PPFE post-autologous PBSCT.

Risk factors for disease progression in Japanese patients with COVID-19 with no or mild symptoms on admission.

BACKGROUND: Although the risk factors for coronavirus disease 2019 (COVID-19) mortality have been identified, there is limited information about the risk factors for disease progression after hospitalization among Japanese patients with COVID-19 exhibiting no or mild symptoms. METHODS: All 302 consecutive patients who were admitted to our institutions and diagnosed with COVID-19 between March and December 2020 were retrospectively assessed. Ultimately, 210 adult patients exhibiting no or mild symptoms on admission were included in the analysis. They were categorized into the stable (no oxygen needed) and worsened (oxygen needed) groups, and their characteristics and laboratory data were compared. RESULTS: Among 210 patients, 49 progressed to a severe disease stage, whereas 161 did not. The mean patient age was 52.14 years, and 126 (60.0%) patients were male. The mean body mass index (BMI) was 23.0 kg/m2, and 71 patients were overweight (BMI ≥ 25 kg/m2). Multivariate logistic analysis showed that old age, overweight, diabetes mellitus (DM), and high serum ferritin levels were independent risk factors for disease progression. CONCLUSIONS: Clinicians should closely observe patients with COVID-19, especially those with risk factors such as old age, overweight, DM, and high serum ferritin levels, regardless of whether they have no or mild symptoms.

Remarkable response to dacomitinib in a patient with leptomeningeal carcinomatosis due to EGFR-mutant non-small cell lung cancer.

Dacomitinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, is a standard therapeutic option for patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, its efficacy in patients with central nervous system lesions is unclear. Here, we describe a case of EGFR-mutant NSCLC whose neurological symptoms were due to leptomeningeal carcinomatosis that was successfully treated with dacomitinib. After initiation of dacomitinib, the neurological symptoms of the patient were remarkably improved and leptomeningeal dissemination and brain metastases were shown to have regressed on magnetic resonance imaging (MRI) scan. To our knowledge, this is the first report showing the efficacy of dacomitinib in a patient with leptomeningeal carcinomatosis due to EGFR-mutant NSCLC. The current case suggests that dacomitinib is a novel treatment option for patients with EGFR-mutant NSCLC accompanied by central nervous system lesions, even those with symptomatic leptomeningeal carcinomatosis. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This is the first report showing the efficacy of dacomitinib in a patient with leptomeningeal carcinomatosis due to EGFR-mutant NSCLC. WHAT THIS STUDY ADDS: The current case suggests that dacomitinib is a novel treatment option for patients with EGFR-mutant NSCLC accompanied by CNS lesions, even in those with symptomatic leptomeningeal carcinomatosis.

Meteorological effects on severe hemoptysis: A hospital-based observational study.

BACKGROUND: Although some meteorological factor are likely to contribute to the onset of hemoptysis, few studies have investigated this issue, with none conducted in the Asia-Pacific region. Therefore, the present study aimed to evaluate the associations of meteorological factors with the occurrence of hemoptysis. Differences in the frequency of hemoptysis among several calendar variables were also assessed. METHODS: A total of 47 hemoptysis patients aged ≥ 20 years undergoing bronchial artery embolization in Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers from January 2012 to December 2017 were included in the study. All hemoptysis events were assembled in a single time series, and the proportion of hemoptysis days was 2.1%. The associations of meteorological variables with hemoptysis days were estimated as odds ratios with 95% confidence intervals by using multivariable-adjusted logistic regression models. The frequency of hemoptysis days was compared among several calendar variables using a chi-square test. RESULTS: Mean relative humidity was negatively associated with hemoptysis (P for trend = 0.02). The inverse association remained significant when only the hemoptysis events with no infectious lung diseases were used (P for trend=0.02). No significant difference was observed in the occurrence of hemoptysis among seasons, months, or other calendar variables (all P ≥ 0.21). CONCLUSIONS: Lower relative humidity was a significant risk factor for the development of hemoptysis. Clinicians should be aware of the potential for increases in hemoptysis events on days with low ambient humidity.