内科: オープンアクセス
オープンアクセス

概要

Cancer Research 2018: Expression of programmed cell death 1 ligands in histiocytic and dendritic cell neoplasms - Jie Xu - The Unviersity of Texas MD Anderson Cancer Center, USA

Jie Xu

PD-1 (programmed cell death protein 1) is ex¬pressed on activated T cells. The ligands (PD-L1 or PD-L2) on tumor cells or antigen presenting cells bind to PD-1 and results in reduced T cell activation and inhibited immune responses. Antibodies tar¬geting PD-1 or PD-L1 elicit antitumor immunity in a subset of patients with solid tumors including mel¬anoma, renal cell carcinoma, non-small cell lung cancer and hematopoietic tumors such as classical Hodgkin lymphoma, and clinical response correlates with PD-1 ligand expression by malignant or immune cells within the tumor microenvironment. Histiocytic and dendritic cell sarcomas are malignant neoplasms with high morbidity and mortality; they are rare and can be difficult to diagnose. We examined the ex-pression of PD-1 ligands on histiocytic and dendritic cell sarcomas. Seven of 14 histiocytic sarcomas (HS) (50%), 2 of 5 interdigitating dendritic cell sarcomas (IDS) (40%), 10 of 20 follicular dendritic cell sarco¬mas (FDS) (50%), and none of 9 blastic plasmacytoid dendritic cell neoplasms (BPDCN) were positive for PD-L1. Eleven of 20 (55%) follicular dendritic cell sar¬comas were also positive for PD-L2. Our results sug¬gest that PD-L1 and PD-L2 IHC may prove useful in establishing or confirming the diagnosis of histiocytic and dendritic cell sarcomas. Given that patients with histiocytic and dendritic cell sarcomas are generally resistant to conventional chemotherapy, checkpoint blockade may prove a more effective alternative. In summary, PD-L1 and PD-L2 are useful new markers for identifying select histiocyte and dendritic cell neoplasms and reveal novel patient populations as rational candidates for immunotherapy. Customized cell passing protein 1, is a protein on the outside of cells that has a job in directing the insusceptible framework’s reaction to the cells of the human body by down-controlling the invulner¬able framework and advancing self-resistance by sti¬fling T cell incendiary action. This forestalls immune system sicknesses, yet it can likewise keep the safe framework from murdering malignant growth cells. PD-1 is an invulnerable checkpoint and watchmen against autoimmunity through two systems. Initial¬ly, it advances apoptosis (customized cell passing) of antigen-explicit T-cells in lymph hubs. Second, it diminishes apoptosis in administrative T cells (miti¬gating, suppressive T cells). PD-1 inhibitors, another class of medications that square PD-1, initiate the safe framework to assault tumors and are utilized to treat specific kinds of malignant growth. The PD-1 protein in people is encoded by the PDCD1 quality. PD-1 is a cell surface receptor that has a place with the immunoglobulin superfamily and is communicat¬ed on T cells and professional B cells. PD-1 ties two ligands, PD-L1 and PD-L2. PD-1 is a sort I film pro¬tein of 288 amino acids. PD-1 is an individual from the all-encompassing CD28/CTLA-4 group of T cell regulators. The protein’s structure incorporates an extracellular IgV area followed by a transmembrane locale and an intracellular tail. The intracellular tail contains two phosphorylation destinations situat¬ed in an immunoreceptor tyrosine-based inhibito¬ry theme and an immunoreceptor tyrosine-based switch theme, which proposes that PD-1 adversely manages T-cell receptor TCR signals. This is predict¬able with authoritative of SHP-1 and SHP-2 phospha¬tases to the cytoplasmic tail of PD-1 upon ligand of¬ficial. Likewise, PD-1 ligation up-directs E3-ubiquitin ligases CBL-b and c-CBL that trigger T cell receptor down-modulation. PD-1 is communicated on the