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.
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.
IntroductionProgrammed 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-1β (IL-1β) plays a key role in regulation of PD-L1 expression in non–small cell lung cancer (NSCLC).MethodsWe performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1β in vitro to elucidate its induction of PD-L1 on NSCLC cells.ResultsThe IL-1β gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1β and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1β 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-1β and IFN-γ.DiscussionOur study reports high levels of IL-1β 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-1β–MAPK axis being a promising therapeutic target for attenuation of PD-L1–mediated suppression of antitumor immunity.
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.
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