Immune Checkpoints and Inhibitors

Abstract

Günümüzde klinik önemi giderek artan tümör immünolojisi ile ilgili çalışmalar ilk olarak 19.yy'da William Coley'in ölü bakteri hücrelerini sarkomlara enjekte ederek tümör boyutlarında küçülme olduğunu göstermesiyle başlamıştır (1). Bu çalışmalar yeni tedavi yaklaşımlarının ve immün denetim noktalarını inhibe eden moleküller gibi yeni ajanların tüm kanser tiplerinde araştırılmasıyla sürmektedir. Klinik uygulamada karşımıza çıkan Antigen-specific T cells encountering and responding to tumor cells are regulated by a variety of mechanisms including inhibitory receptors and regulatory T cells to prevent overexposure immune responses. These regulatory mechanisms, so called ''immune checkpoints'', suppress T cell response. Thus, it prevents tissue damage and the development of autoimmunity by preventing an excessive immune response. Immune checkpoint inhibitors are increasingly used in clinical practice and have become part of the standard treatment approach for the treatment of various tumor types. These agents are antibody-based treatments targeting cytotoxic T-lymphocyte antigen-4, programmed cell death-1 and programmed cell death ligand-1. They have been used in the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, and some other tumor types. The incidence of toxicities has expanded with increasing clinical use. The side effects resulting from the immunological effects of these treatments are called ''immune-related adverse events'' and affect many organs in a wide spectrum, unlike conventional chemotherapy side effects. In order to understand the mechanisms of action and side effects of these therapies, which are more frequently encountered in clinical practice, it is necessary to understand immune checkpoints and inhibitors. In this review, receptors that function as immunological checkpoints, as well as the drugs targeting them, are described.

The relation of CD3, CD4, CD8 and PD-1 expression with tumor type and prognosis in epithelial ovarian cancers

“…The ligand commonly found in tumor cells is PD-L1. PD-L1, expressed in the micro-environment of the tumor, suppresses the immune response developing against the tumor [10]. PD-L1 is thought to play a role in the immunological escape mechanism that causes tumor cell growth, proliferation and metastasis [2].…”