Establishing a whole blood CD4 T cell immunity measurement to predict response to anti-PD-1.

Background: Biomarkers that can accurately predict the efficacy of immune checkpoint inhibitors (ICIs) against programmed death 1 (PD-1) ligand in cancer immunotherapy are urgently needed. We have previously reported a novel formula that predicts the response to treatment with second-line nivolumab with high sensitivity and specificity in patients with non-small cell lung cancer (NSCLC) previously treated with chemotherapy. The formula was based on the percentages of CD62LCD4 T cells (effector T cells; %Teff) and CD4CD25FOXP3 T cells (regulatory T cells; %Treg) in the peripheral blood before treatment estimated using the peripheral blood mononuclear cell (PBMC) method.

Single-Cell Analysis Reveals a CD4+ T-cell Cluster That Correlates with PD-1 Blockade Efficacy.

Unlabelled: CD4+ T-cell immunity helps clonal proliferation, migration, and cancer cell killing activity of CD8+ T cells and is essential in antitumor immune responses. To identify CD4+ T-cell clusters responsible for antitumor immunity, we simultaneously analyzed the naïve-effector state, Th polarization, and T-cell receptor clonotype based on single-cell RNA-sequencing data. Unsupervised clustering analysis uncovered the presence of a new CD4+ T-cell metacluster in the CD62Llow CD4+ T-cell subpopulation, which contained multicellular clonotypes associated with efficacy of programmed death-ligand 1 (PD-1) blockade therapy.

Combination of immune check inhibitor and immunomodulatory arabinomannan extracted from : A case report.

The present study selected two patients with lung cancer and epidermal growth factor receptor () mutations who were treated with a programmed cell death protein 1 (PD-1) antibody and an immunomodulatory arabinomannan extracted from . In the first case, a 67-year-old female was diagnosed with lung adenocarcinoma with an mutation (exon 19 deletion) and Stage IVB disease. Initial treatment with an mutation-targeted tyrosine kinase inhibitor (TKI), erlotinib, demonstrated a partial response.

Chemoradiotherapy followed by durvalumab in patients with unresectable advanced non-small cell lung cancer: Management of adverse events.

Background: Chemoradiotherapy followed by durvalumab is the standard treatment for the patients with local advanced non-small cell lung cancer (NSCLC). There is a real-world data about the management of adverse events, such as pneumonitis, according to the different institutions. Here, we present the experience regarding the management of adverse events after the initiation of durvalumab as daily practice.

Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non-small cell lung cancer harboring EGFR mutation.

Background: Osimertinib is the most promising treatment option for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) with acquired T790M resistance. However, recent studies have suggested that osimertinib could increase the frequency of serious adverse events (AEs) if administered immediately after immune checkpoint inhibitor (ICI) treatment.

Methods: In this single-institution retrospective study conducted from May 2016 to January 2019, osimertinib was administered to 47 patients with pretreated advanced NSCLC harboring the EGFR mutation.

CD4 T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy.

Accumulating evidence indicates that CD8 T cells in the tumor microenvironment and systemic CD4 T-cell immunity play an important role in mediating durable antitumor responses. We longitudinally examined T-cell immunity in the peripheral blood of patients with non-small lung cancer and found that responders had significantly ( < 0.0001) higher percentages of effector, CD62L CD4 T cells prior to PD-1 blockade.

Correction to: Re-challenge of afatinib after 1st generation EGFR-TKI failure in patients with previously treated non-small cell lung cancer harboring EGFR mutation.

In the original publication of the article, the authors found few errors and the corrections are given below.

Clinical difference between discontinuation and retreatment with nivolumab after immune-related adverse events in patients with lung cancer.

Background: After the cessation of immune checkpoint inhibitor (ICI) therapy due to an immune-related adverse event (irAE), it remains unclear whether retreatment with ICI is more effective than its discontinuation. To explore the clinical significance of its retreatment, patients with non-small cell lung cancer (NSCLC) who had treatment interruption of nivolumab due to irAEs were identified and the clinical differences between discontinuation and retreatment with nivolumab were retrospectively reviewed.

Methods: 49 (26%) of 187 patients treated with nivolumab experienced the cessation of treatment due to a serious irAE.

Radiotherapy is an independent prognostic marker of favorable prognosis in non-small cell lung cancer patients after treatment with the immune checkpoint inhibitor, nivolumab.

Background: It remains unclear why radiation clinically provides a synergistic effect when combined with immune checkpoint inhibitors such as nivolumab. The purpose of our study was to retrospectively evaluate whether the therapeutic efficacy of nivolumab is improved as a result of a history of radiotherapy (RT) in patients with previously treated advanced non-small cell lung cancer (NSCLC).

Methods: From February 2016 to December 2017, 124 consecutive patients were administered nivolumab for pretreated advanced NSCLC.

Different incidence of interstitial lung disease according to different kinds of EGFR-tyrosine kinase inhibitors administered immediately before and/or after anti-PD-1 antibodies in lung cancer.

Background: The aim of our study was to retrospectively assess the incidence of interstitial lung disease (ILD) related to EGFR-tyrosine kinase inhibitor (TKI) treatment immediately before and/or after the administration of a PD-1 antibody.

Methods: We analyzed the data of 26 patients who underwent treatment with EGFR-TKIs immediately before and/or after the administration of an anti-PD-1 antibody.

Results: Four out of the 26 patients developed ILD during EGFR-TKI treatment: three patients during the administration of osimertinib immediately after, and one during afatinib immediately before treatment with an anti-PD-1 antibody.

Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non-small cell lung cancer patients.

Background: It is unclear whether the chemotherapy response improves after exposure to immunotherapy. Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects that stimulate tumor shrinkage. We conducted a retrospective study to evaluate improvement of the efficacy of ramucirumab plus docetaxel after the failure of nivolumab as a PD-1 inhibitor.

Re-challenge of afatinib after 1st generation EGFR-TKI failure in patients with previously treated non-small cell lung cancer harboring EGFR mutation.

Background: Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure.

Methods: From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study.

Combination therapy with carboplatin and paclitaxel for small cell lung cancer.

Background: Although small cell lung cancer (SCLC) is an aggressive cancer, few useful treatment options exist after relapse. Information concerning the efficacy and safety of carboplatin plus paclitaxel in patients with SCLC is limited.

Methods: From April 2007 to October 2016, 318 patients with SCLC received chemotherapy at our institution.

Eosinophil transendothelial migration induced by the bronchoalveolar lavage fluid of acute eosinophilic pneumonia.

Background And Objective: Acute eosinophilic pneumonia (AEP) is characterized by a massive pulmonary infiltration of eosinophils. Mechanisms regulating the selective accumulation of eosinophils in AEP have not been fully established. The objective of this study was to evaluate the mechanisms of eosinophil accumulation in alveolar spaces through examination of bronchoalveolar lavage fluid (BALF) from AEP patients (AEP-BALF).

Trans-basement membrane migration of eosinophils induced by LPS-stimulated neutrophils from human peripheral blood .

In the airways of severe asthmatics, an increase of neutrophils and eosinophils is often observed despite high-dose corticosteroid therapy. We previously reported that interleukin-8-stimulated neutrophils induced trans-basement membrane migration (TBM) of eosinophils, suggesting the link between neutrophils and eosinophils. Concentrations of lipopolysaccharide (LPS) in the airway increase in severe asthma.

Mycobacterium gordonae-induced humidifier lung.

Background: Nontuberculous mycobacteria are well known to be a cause of hot tub lung, however, to our knowledge, there exists no case report of humidifier lung induced by mycobacteria.

Case Presentation: A case of a nonimmunocompromised female patient with Mycobacterium gordonae-induced humidifier lung is described. She spontaneously recovered after discontinuing ultrasonic humidifier use.

[Rapid specific IgE assay (ImmunoCAP® RAPID) and skin prick test in the diagnosis of allergic disease].

Background: ImmunoCAP® Rapid is a rapid test kit to measure the allergen-specific IgE to the eight major inhalation allergen (cat, mite, orchard grass, ragweed, wormwood, dog, cockroach, Japan cedar).

Methods: We performed ImmunoCAP® Rapid 83 patients with allergic disease (26 males, 57 females, median aged 43 years, 53 of asthma, 43 of allergic rhinitis) in our allergy center. ImmunoCAP® Rapid results were compared with those of skin prick test (SPT).

Omalizumab attenuates airway inflammation and interleukin-5 production by mononuclear cells in patients with severe allergic asthma.

Background: Omalizumab, an anti-immunoglobulin E monoclonal antibody, has shown an inhibitory effect on airway inflammation, which may be associated with clinical improvement of severe asthma. This study evaluated changes in airway inflammation and cytokine release by the peripheral blood mononuclear cells (PBMCs) of Japanese patients with severe asthma after administration of omalizumab.

Methods: Sixteen Japanese patients with severe asthma who were allergic to house-dust mites were enrolled in this study.

Effect of formoterol on eosinophil trans-basement membrane migration induced by interleukin-8-stimulated neutrophils.

Background: Neutrophils are often increased in the airways of either chronic severe asthma or acute exacerbations. Neutrophils that have migrated in response to interleukin-8 (IL-8) may lead eosinophils to accumulate in the airways of patients with asthma and possibly aggravate the disease. In this study, we investigated whether formoterol modified the trans-basement membrane migration (TBM) of eosinophils stimulated with neutrophils and IL-8.

[Effects of educational guidance on airway inflammation of patients with severe persistent asthma].

Background: Airway inflammation is a fundamental feature of bronchial asthma. We examined whether educational guidance using a text on pathophysiology and management of asthma modify airway inflammation of severe asthma.

Methods: Eighteen severe persistent asthmatics were enrolled in this study.

[A case of bronchial asthma caused by occupational exposure to trichophyton].

A case involved a 39-year-old female nurse in a health-care facility for elderly individuals requiring long-term care, who presented with insufficient control of bronchial asthma. Although she did not have tinea, she had opportunities for contact with patients who did. Careful interview of history suggested a relationship between asthma exacerbation and workplace, so we measured the specific IgE antibody to Trichophyton and confirmed a positive result.

[Questionnaire for determining relationship between nasal and asthma symptoms].

Background: The interaction between allergic rhinitis and bronchial asthma is well known. However, there is little epidemiological data on the relationship between nasal diseases and asthma, especially in Japan.

Methods: We administered a questionnaire to 126 patients to examine the frequency of associations between nasal and asthma symptoms in patients with both nasal disease and asthma.

Changes in airway inflammation and hyperresponsiveness after inhaled corticosteroid cessation in allergic asthma.

Background: Most patients with asthma are currently controlled by pharmacotherapeutic means such as inhaled corticosteroid (ICS). However, whether ICS actually induces remission of asthma remains unknown. The present study evaluates changes in airway inflammation and hyperresponsiveness in adult patients with asthma after stopping ICS.