RESUMEN
Diabetic foot is one of the most common complications of diabetic mellitus (DM). This DM patient was admitted to our hospital presented with a 2-month history of plantar lesion. Shortly afterward, the patient appeared hemoptysis, respiratory failure, and multiple purpuric papules on his limbs. Biopsy of left plantar lesions demonstrated angiosarcoma. Therefore, it is suggested that tissue biopsy should be taken as early as possible for DM patients with prolonged nonhealing wounds.
Asunto(s)
Pie Diabético , Hemangiosarcoma , Humanos , Hemangiosarcoma/complicaciones , Hemangiosarcoma/diagnóstico , Pie Diabético/diagnóstico , BiopsiaRESUMEN
Chimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in B cell malignancies. However, high tumor burden limits clinical efficacy and increases the risk of cytokine release syndrome and neurotoxicity, which is associated with over-activation of the CAR-T cells. The hinge domain plays an important role in the function of CAR-T cells. We hypothesized that deletion of glycine, an amino acid with good flexibility, may reduce the flexibility of the hinge region, thereby mitigating CAR-T cell over-activation. This study involved generating a novel CAR by deletion of two consecutive glycine residues in the CD8 hinge domain of second-generation (2nd) CAR, thereafter named 2nd-GG CAR. The 2nd-GG CAR-T cells showed similar efficacy of CAR expression but lower hinge flexibility, and its protein affinity to CD19 protein was lower than that of 2nd CAR-T cells. Compared to the 2nd CAR-T cells, 2nd-GG CAR-T cells reduced proinflammatory cytokine secretion without diminishing the specific cytotoxicity toward tumor cells in vitro. Furthermore, 2nd-GG CAR-T cells prolonged overall survival in an immunodeficient mouse model bearing NALM-6 when tumor burden was high. This study demonstrated that a lower-flexibility of CD8α hinge improved survival under high tumor burden and reduced proinflammatory cytokines in preclinical studies. While there is potential for improved safety and efficacy, yet this needs validation with clinical trials.
Asunto(s)
Antígenos CD8/inmunología , Citocinas/metabolismo , Leucemia Linfocítica Crónica de Células B/terapia , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Animales , Antígenos CD19/genética , Antígenos CD19/inmunología , Antígenos CD8/genética , Línea Celular Tumoral , Femenino , Humanos , Inmunoterapia Adoptiva/métodos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Transfusión de Linfocitos , Ratones , Ratones SCID , Receptores Quiméricos de Antígenos/genética , Análisis de Supervivencia , Linfocitos T/citología , Linfocitos T/trasplante , Transducción Genética , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Immune checkpoint inhibitor (ICI)-related massive hemoptysis with cavitation has rarely been identified. Here, we report a case of advanced lung adenocarcinoma with lethal bleeding after eight cycles of pembrolizumab. A 55-year-old male was diagnosed with stage IV non-small cell lung cancer (NSCLC). Following confirmation of high programmed death-ligand 1 (PD-L1) expression of 60% cancer cells, he subsequently received pembrolizumab monotherapy. His symptoms and chest images significantly improved after four cycles of therapy. However, after eight cycles of immunotherapy, he presented with recurrence of bloody sputum and shortness of breath. Pembrolizumab was discontinued and a diagnosis of checkpoint inhibitor-associated pneumonitis (CIP) was made. When the CIP was absorbed after glucocorticoid therapy, the patient died of sudden massive hemoptysis with cavitation in the lesion. KEY POINTS: Although checkpoint inhibitor associated pneumonitis was the leading cause of ICI-related death, clinicians should be alerted to the finding that more attention should be given to hemoptysis attributed to ICI therapy in advanced lung cancer.