Several recent studies have shown that salvage chemotherapy following PD‐1 blockade produces high antitumor activity in some patients with non‐small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil‐to‐lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid‐derived suppressor cells and tumor‐associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time‐series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non‐responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non‐responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD‐1 blockade and chemotherapy.

Little is known about the anti‐tumor activity of humoral immunity in lung cancer patients treated with nivolumab, an immune checkpoint inhibitor. Herein, we report a case of lung cancer with 5% expression of PD‐L1, in which a partial response to nivolumab was sustained for > 7 months. Immunohistochemical analysis of the metastatic lymph node biopsy specimen showed prominent accumulation of plasma cells and immunoglobulin G. These findings suggest that pre‐existing humoral immunity may be worth considering as a candidate therapeutic biomarker of nivolumab in some lung cancer patients.

BackgroundThe combination of PD‐1 inhibitors and cytotoxic drugs is reported to enhance anti‐tumor activity in non‐small cell lung cancer; however, the underlying synergistic mechanisms remain uncertain. This retrospective case series was designed to investigate objective response and survival rates of salvage chemotherapy following nivolumab and explore the immunohistochemical profiles of tumor‐infiltrating immune cells.MethodsThe medical records of 37 patients administered nivolumab were retrospectively reviewed. Overall response rate and progression‐free survival were compared among three groups: salvage chemotherapy following nivolumab, nivolumab therapy alone, and chemotherapy preceding nivolumab.ResultsEight cases met the study criteria. Salvage chemotherapy following nivolumab improved the overall response rate to 62.5% (95% confidence interval [CI] 34.4–90.6%; P = 0.004) and median progression‐free survival to six months (95% CI 4.6–7.4; P = 0.016), compared to nivolumab alone and preceding chemotherapy. The response to salvage chemotherapy was not associated with tumor PD‐L1 expression. A partial response was achieved in four cases with ≤ 5% and ≤ 2.9 cells/mm2 of PD‐1+ immune cells, whereas stable disease and progressive disease were observed in three cases with ≥ 30% and ≥ 12.7 cells/mm2. Responders had fewer PD‐1+ immune cells than non‐responders (percentage P = 0.028; density P = 0.034).ConclusionSalvage chemotherapy following nivolumab improved anti‐tumor activity regardless of tumor PD‐L1 status, but nivolumab following chemotherapy did not. The presence of few PD‐1+ tumor‐infiltrating immune cells may serve as a potential predictor of response to salvage chemotherapy. Further studies involving a large cohort are needed to clarify how nivolumab re‐sensitizes the tumor immune microenvironment to chemotherapy.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. Case presentation: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus. It involves multiple organ systems, including the lungs. However, the significance of the lung involvement in SFTS remains unclear. In the present study, we aimed to investigate the relationship between the clinical findings and abnormalities noted in the chest computed tomography (CT) of patients with SFTS. The medical records of 22 confirmed SFTS patients hospitalized in five hospitals in Nagasaki, Japan, between April 2013 and September 2019, were reviewed retrospectively. Interstitial septal thickening and ground-glass opacity (GGO) were the most common findings in 15 (68.1%) and 12 (54.5%) patients, respectively, and lung GGOs were associated with fatalities. The SFTS patients with a GGO pattern were elderly, had a disturbance of the conscious and tachycardia, and had higher c-reactive protein levels at admission (p = 0.009, 0.006, 0.002, and 0.038, respectively). These results suggested that the GGO pattern in patients with SFTS displayed disseminated inflammation in multiple organs and that cardiac stress was linked to higher mortality. Chest CT evaluations may be useful for hospitalized patients with SFTS to predict their severity and as early triage for the need of intensive care.