Receptor programowanej smierci PD-1 jako potencjalny cel w terapii przeciwnowotworowej

Abstract

Author(s): Monika Pilecka, Anna Brzozowska, Maria Mazurkiewicz

Nowadays, an improved understanding of the molecular mechanisms ruling the host immune response to tumors has led to the identification of checkpoint signaling pathways involved in limiting the anticancer immune response. One of the most significant checkpoint pathways responsible for mediating tumor-inducted immune suppression is the programmed death-1 (PD- 1) pathway, which is normally involved in promoting tolerance and preventing tissue damage during chronic inflammation. The programmed death-1 receptor is upregulated in activated T lymphocytes and inhibits T-cell function upon binding to its ligands B7-H1 (PD-L1) and B7-DC (PD-L2). Many solid tumors express PD ligand 1 (PD-L1) and this is often associated with a worse prognosis. Tumor-infiltrating lymphocytes from patients with cancer typically express PD-1 and have impaired antitumor functionality. Proof-of-concept has come from several preclinical studies in which blockade of PD-1 or PD-L1 enhanced T-cell function and tumor cell lysis. Three monoclonal antibodies against PD-1, and one against PD-L1, have reported phase 1 data. All four agents have shown encouraging preliminary activity, and those that have been evaluated in larger patient populations appear to have encouraging safety profiles. If subsequent investigations confirm the initial results, it is conceivable that agents blocking the PD-1/PD-L1 pathway will prove valuable additions to the grooving armamentarium of immunotherapeutic agents.

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