İmmün Denetim Noktaları ve İnhibitörleri

Abstract

Tümör hücreleri ile karşılaşan ve yanıt oluşturan antijen spesifik T hücreleri, aşırıya kaçan immün yanıtları önlemek için inhibitör reseptörler ve regülatuar T hücreleri olmak üzere çeşitli mekanizmalar tarafından düzenlenir. ‘‘İmmün denetim noktaları’’ olarak adlandırılan bu düzenleyici mekanizmalar, T hücre yanıtını baskılar. Böylece aşırıya kaçan immün yanıtı engelleyerek doku hasarı ve otoimmünite gelişimini önler. İmmün denetim noktası inhibitörleri klinik pratikte giderek daha fazla kullanılmaktadır ve çeşitli tümör tiplerinin tedavisinde standart tedavi yaklaşımının bir parçası haline gelmiştir. Bu ajanlar sitotoksik T-lenfosit antijeni 4’ü, programlanmış hücre ölümü 1’i ve programlanmış hücre ölümü ligandını hedef alan antikor bazlı tedavilerdir. Melanom, renal hücreli karsinom, küçük hücreli dışı akciğer kanseri ve diğer bazı tümör tiplerinin tedavisinde kullanılmaktadır. Klinik kullanımlarının artmasıyla, toksisitelerinin görülme sıklığı da artış göstermiştir. Bu tedavilerin immünolojik etkilerinin bir sonucu olarak ortaya çıkan yan etkiler ‘‘immün ilişkili advers olaylar’’ olarak adlandırılır ve birçok organı alışılmış kemoterapi yan etkilerinden farklı olarak geniş bir spektrumda etkilemektedir. Klinik pratikte daha sık karşılaşmaya başladığımız bu tedavilerin etki mekanizmalarını ve yan etkilerini anlayabilmek için immün denetim noktaları ve inhibitörlerinin anlaşılması gereklidir. Bu derlemede immün denetim noktaları olarak işlev gören reseptörler ve onları hedef alan ilaçlardan bahsedilmiştir.

Keywords

• PD-1
• PD-L1
• CTLA-4
• Kanser
• İmmünoterapi

Immune Checkpoints and Inhibitors

Abstract

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.

Keywords

• PD-1
• PD-L1
• CTLA-4
• Cancer
• Immunotherapy

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