BACKGROUND: Nivolumab is an checkpoint inhibitor combining with programmed death-1 (PD-1) receptor on T cells, which can block the interactions between PD-1 and programmed death ligands (PD-L), including PD-L1 and PD-L2. And then block the immunosuppression mediated by the PD-1 pathway. The aim of the study is to investigate the clinical manifestations, diagnosis, treatment and prognosis of treatment-related skin toxicity caused by PD-1 inhibitor Nivolumab. METHODS: The clinical data of treatment-related skin toxicity caused by PD-1 inhibitor Nivolumab in a patient with advanced lung adenocarcinoma admitted to the Shanghai Chest Hospital was retrospectively analyzed. The diagnosis, treatment and prognosis of the patient were discussed. RESULTS: The patient was a 60-year-old male presented with relapse after surgery and adjuvant postoperative chemotherapy for his lung carcinoma. The patient's condition still progressed after multiple chemotherapy, targeted therapy and local radiotherapy of bone metastasis. Then Nivolumab, a kind of PD-1 inhibitors, was given intravenously every 3 weeks with the average dosage 3 mg/kg. After one cycle of Nivolumab, the patient began to have skin rashes, which aggravated gradually. The patient's skin toxicity was alleviated after enough steroids and was controlled with tapering steroids slowly. Now the patient was still given oral steroids treatment. And the lung disease remained stable. CONCLUSIONS Immune-related skin toxicity associated with PD-1 inhibitor should be aware of; early detection, early treatment and the prognosis could be better. It is necessary to improve the understanding of Immune-related skin toxicity associated with PD-1 inhibitor, to diagnose and treat it early, and the prognosis could be better.
Adenocarcinoma of Lung ; drug therapy ; Humans ; Male ; Middle Aged ; Nivolumab ; adverse effects ; pharmacology ; therapeutic use ; Prognosis ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors ; Skin ; drug effects

Objective: To Evaluation the effect of PD-1 inhibitor Nivolumab on the proliferation and cytotoxicity of anti-CD19 chimeric antigen receptor T cells (CD19-CAR-T) in vitro. Methods: Five patients with high PD-1 expression in peripheral blood and five healthy volunteers were selected. These peripheral blood mononuclear cells were used as the source of T cells to prepare CD19-CAR-T cells. Different doses (72, 36, 18 μg/ml) of Nivolumab was added on day 8 to the culture medium. Patient T cells incubated with 72 μg/ml Nivolumab and CD19-CAR-T cells of healthy volunteers were used as controls. CCK-8, lactate dehydrogenase (LDH) cytotoxicity assay and ELASA were used to detect the proliferation capacity, the specific cytotoxicity and the inflammatory factor secretion. Results: ①T cells from patients with high expression of PD-1 as the source of CD19-CAR-T cells did not affect transfection rate compared with that of healthy volunteers [(32.80±7.22)% vs (35.10±5.84)%, t=-0.554, P=0.593]. ②Incubation of CD19-CAR-T cells with 72 μg/ml Nivolumab did not affect CD19-CAR-T cell proliferation, but its cytotoxicity was significantly higher than that of CD19-CAR-T cells alone or patients' T cells +72 μg/ml Nivolumab (all P<0.001), there was no significant difference in the killing activity between the 72 μg/ml and 36 μg/ml Nivolumab treated CD19-CAR-T cells on Pfeiffer cells (P=0.281, 0.267, respectively), and they were all higher than those of 18 μg/ml Nivolumab treated CD19-CAR-T cells (all P<0.001). ③Different doses of PD-1 inhibitor Nivolumab combined with CD19-CAR-T cells does not affect the secretion of IFN-γ and IFN-α (all P>0.05). Conclusion: Combination of 36 μg/ml PD-1 inhibitor and CD19-CAR-T cells could reduce the drug toxicity and enhance the cytotoxicity.
Antigens, CD19 ; Cell Proliferation ; Humans ; Leukocytes, Mononuclear ; Nivolumab/pharmacology* ; Programmed Cell Death 1 Receptor ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes