PDCD1
小结
PDCD1编码蛋白（程序性细胞死亡蛋白1）PD1，其是在T细胞和祖B细胞上表达的共抑制受体，属于免疫球蛋白超家族。PD1通过结合在其他正常或恶性细胞上表达的配体PD-L1和PD-L2来抑制免疫应答。PD-L1与PD1结合导致抗原特异性T细胞的程序性细胞死亡并且调节性T细胞的细胞凋亡减少，这导致免疫应答的总体下降。PD1的扩增或过表达在某些肿瘤类型中已被鉴定，过表达PDCD1以逃避抗肿瘤免疫应答，并可预测对免疫治疗的反应。抗PD1治疗在表达PD1的癌症中已经成功。
PDCD1 is a key mediator of immune self tolerance and several cancer entities highly express PDCD1 to evade anti-tumoral immune response. Anti-PD1 therapy has been successful in PD1 expressing cancer. PDCD1 (Programmed cell death protein 1) encodes the protein PD1, which is a coinhibitory receptor expressed on T-cells and pro-B cells that belongs to the immunoglobulin superfamily. PD1 acts to inhibit an immune response by binding to the ligands PD-L1 and PD-L2, which are expressed on other normal or malignant cells. PD-L1 binding to PD1 leads to programmed cell death in antigen-specific T-cells and reduced apoptosis in regulatory T-cells, which results in an overall decrease in immune response. Amplification or overexpression of PD1 has been identified in some tumor types and can be predictive of responses to immunotherapy. Antibodies targeting PD1 have been developed and assessed in clinical trials that block the immune evasive PD-L1/PD1 interaction. Atezolizumab, a monoclonal antibody targeting PD-L1, is FDA approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. Pembrolizumab, an anti-PD-1 antibody, is considered first-line therapy for patients with non-small cell lung cancer and metastatic melanomas that express PD-L1 and may be efficacious in other tumors that express PD-L1. Nivolumab, an FDA-approved monoclonal antibody that targets PD-1, is also effective in tumors with high PD-L1 expression due to the blockade of the PD-1/PD-L1 interaction and activation of a robust immune response. Tumors with defects in mismatch-repair and overexpression of PD-L1 should be considered for PD-1 blockade.