No abstract

Anti-programmed cell death-1 (PD-1) agents enhance the antitumor immunoresponse. A number of reports have indicated that patients with malignancies who receive anti-PD-1 agents are at risk for tuberculosis (TB) infection. In this report, we present a patient with non-small cell lung cancer who developed pulmonary tuberculosis while receiving the anti-PD-1 agent nivolumab, and who subsequently demonstrated a paradoxical response (PR) 10 days after initiation of anti-MTB treatment. We suggest that anti-PD-1 agents not only induce the development of pulmonary TB, but also development of PR after anti-MTB treatment, through upregulation of the immune response. Furthermore, based on their radiological and immunological similarity, we speculate that the schema of development of PR closely resembles that of pseudoprogression in non-small cell lung cancer patients after anti-PD-1 treatment.

Background/Aim: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFNγ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). Patients and Methods: IGR was measured using enzymelinked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. Results: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. Conclusion: IFN-γ levels could be a biomarker for ICI-Tx. After the programmed cell death-1 (PD-1) gene was cloned (1), an anti-PD-1 antibody (2) was rapidly developed as an immune checkpoint inhibitor (ICI). ICIs have since become very important anticancer agents (3-5). However, there is currently no other biomarker for non-small-cell lung cancer (NSCLC) than programmed deathligand 1 (PD-L1) (6). Recently, we have reported on NSCLC patients who developed pulmonary Mycobacterium tuberculosis (MTB) infection while receiving nivolumab (7). We have shown that the development of this paradoxical response closely resembles that of pseudo progression after ICI treatment. Furthermore, several studies (8-10) have indicated that the PD-1/PD-L1 axis and interferon-gamma (IFN-γ) are very important for cellular immunity to MTB. The interferon-gamma release assay (IGRA) is widely used as a diagnostic method for latent MTB infection (11). The QuantiFERON ®-TB Test is an IGRA that can measure IFN-γ released from T lymphocytes by whole bloodbased enzyme-linked immunosorbent assay (ELISA). We hypothesized that changes in the PD-1/PD-L1 axis by ICI treatment affect IFN-γ release by T lymphocytes. Thus, the aim of the present prospective observational study was to verify our hypothesis and to examine the usefulness of monitoring IFNγ as a biomarker in patients with NSCLC who are receiving ICI treatment. Patients and Methods Ethics. This study was approved by our institutional review board (approval no.: 884). All patients who participated in this study were enrolled after providing their written informed consent. Furthermore, this study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031881).

Background/Aim: Extracellular water-to-total body water ratio (ECW/TBW) measured by bioelectrical impedance analysis (BIA) reportedly predicts clinical outcomes of various diseases. The aim of this retrospective study was to examine the association between ECW/TBW and therapeutic durability of chemotherapy and/or immune checkpoint inhibitors in advanced lung cancer. Patients and Methods: Patients with advanced lung cancer underwent BIA before chemotherapy and/or treatment with immune checkpoint inhibitors at our hospital between June 2018 and November 2019. Results: Of 75 patients, 18 with ECW/TBW ≥0.4 were assigned to the overhydrated group (OH-G) and 57 patients ECW/TBW <0.4 were assigned to the non-overhydrated group (NOH-G). The median time-to-treatment failure was significantly shorter in the OH-G than in the NOH-G (p=0.003). Multivariate analysis revealed that ECW/TBW ≥0.4 predicted treatment failure [hazard ratio (HR)=2.508, 95% confidence interval (CI)=1.19-5.27; p=0.01]. Conclusion: The ECW/TBW may be an objective parameter for predicting therapeutic durability in advanced lung cancer.

Osimertinib monotherapy is less effective in patients with NSCLC with pleural effusions.