肿瘤免疫治疗进展.pptx

Incorporating Immune-Checkpoint Inhibitors?into?Systemic Therapy of NSCLC;1. Introduction;Immune - checkpoint and their blockers [CTLA4] —— Ipilimumab [PD-1] —— Nivolumab [PDL-1] —— BMS-936559 Advantages: mild toxicity; sustained immune-mediated tumor control. Disadvantages: limited proportion of responders ;Combination leads to synergistic activity NSCLC conventional therapies are capable of modulating the immune system. Conventional and targeted therapies can induce rapid tumor lysis, and immune -checkpoint blockade can then help to induce a sustained immune-mediated tumor control. ;2. Immune Checkpoints and Their Blockade ; PD-1/PD-L1 —— Programmed cell death protein 1 and its ligand PD -1 negatively regulates the activation of T cells in peripheral tissues and is expressed by activated T cells. PD-L1 is one of ligands binding to PD-1 and expressed on antigen presenting cells but also on cancer cells.;;Block immune-checkpoint ;Immunosuppressive Factors Present in the Tumor Microenvironment; 2.2 Monoclonal Antibodies Targeting Immune-Checkpoint;; Four distinct response patterns induced by immune-checkpoint inhibitors always result in : (a) shrink-age in baseline lesions, without new lesions; (b) durable stable disease (followed by a slow, steady decline); (c) response after an increase in total tumor burden; (d) response in the presence of new lesions.;Ipilimumab —— Anti -CTLA4 antibodies ;Paclitaxel 175mg/m2 Carboplatin AUC 6 q21d Ipilimumab 10mg/kg q21d placebo 10mg/kg q21d;Result:; The ir-PFS was improved in patients receiving the phased schedule versus chemotherapy alone (HR, 0.72; P = .05). The concurrent schedule did not improve the ir-PFS. The median OS of 12.2 months for in the phased ipilimumab arm was similar to that reported for the combination of paclitaxel and carboplatin with bevacizumab (12.3months).;Histology might be a predictive factor In the phased ipilimumab arm, improv