Kanser immünoterapisinde güncel yaklaşımlar ve immünoterapinin sınırlayıcı etkilerine genel bakış

Year 2022, , 153 - 165, 26.03.2022

Gül Koca , Sakou Seydou Özlem Yıldırım

https://doi.org/10.18663/tjcl.1038881

Abstract

Günümüzde ileri evre kanserlerin tedavisindeki güçlükler henüz aşılamamıştır. Kemoterapi ve radyoterapdeki ilerlemelere rağmen, geleneksel kanser tedavisi, tümör ilerlemesini kontrol etmede yetersiz kalmakta ve tümör hücresinin ilaç direnci geliştirmesi ile tedavinin başarısı sınırlanmaktadır. Bu durum daha iyi tedavi seçeneklerinin araştırılmasını zorunlu kılmaktadır. İmmün kontrol noktası sinyallerini hedefleyen ilaçlar, immün sistem ile tümör arasındaki etkileşimlerin klinik önemini güçlendirerek, immün sistemin anti kanser aktivite göstermesini sağlanmaya çalışarak,kanser tedavisine yeni bir yaklaşım getirmiştir. İmmün sistem ve kanserle ilgili temel mekanizmaları hakkındaki bilgiler hızla artmaktadır. İmmün sistem, kendini ve kendinden olmayanı ayırt edecek şekilde tasarlanmıştır ve genetik rekombinasyon yoluyla tanıyabileceği antijen sayısı neredeyse sınırsızdır. Bu nedenle kanser hücrelerindeki mutasyonel olaylar, anormallikler ve farklılıklar kanserin gelişmesini veya ilerlemesini önlemede önemli bir rol oynayabilir. Bununla birlikte, tümörler immünsürvayanstan kaçmak için çeşitli mekanizmalar kullanabilir. İmmünoterapinin gelişimi büyük umut vadetse de, hastaların bir kısmında primer direnç gelişebilmekte ve bu hastalar immünoterapiden fayda görmemektedirler. Ayrıca, tedaviye yanıt veren hastalarda da klinik ilerlemede ortaya çıkabilen kazanılmış direnç, immünoterapinin başarısını sınırlayabilmektedir. Direnç mekanizmaları arasında, tümör mikro çevresindeki (TME) immün hücrelerinin işlevinin ve infiltrasyonunun azalmasına yol açan tümöre özgü yollar vardır. Direnç başlangıcını önlemek ve üstesinden gelmek için kemoterapi, radyoterapi ve yeni immünomodülatör ajanlarla kombinasyon tedavilerini öngören yeni stratejiler umut vericidir. Bu derlemede, immünoterapötik yaklaşımlar (İmmün Kontrol Noktası İnhibitörleri (ICI), Lenfosit- Düzenleyici Sitokinler, Kanser Aşıları, CAR T ve T Hücre Reseptörü (TCR), KostimülatörReseptörler), kanser immünoterapisi ile ilgili mevcut bilgiler ve immunoterapiye verilen hasta yanıtlarının incelenmesi hedeflenmiştir.

Keywords

Kanser immünoterapi, immün kontrol noktası inhibitörleri, lenfosit- düzenleyici sitokinler, kanser aşıları, CAR T ve T hücre reseptörü

Overview of current approaches in cancer immunotherapy and limiting effects of immunotherapy

Abstract

Today, the difficulties in the treatment of advanced cancers have not been overcome yet. Despite advances in chemotherapy and radiotherapy, conventional cancer treatment remains insufficient to control tumor progression, and the success of treatment is limited by the tumor cell's development of drug resistance. This situation necessitates the search for better treatment options. Drugs targeting immune checkpoint signals have brought a new approach to cancer treatment by strengthening the clinical importance of interactions between the immune system and the tumor, and by trying to ensure that the immune system shows anti-cancer activity. Information about the immune system and its basic mechanisms related to cancer is increasing rapidly. The immune system is designed to distinguish between self and non-self, and the number of antigens it can recognize through genetic recombination is almost unlimited. Therefore, mutational events, abnormalities and differences in cancer cells can play an important role in preventing the development or progression of cancer. However, tumors can use a variety of mechanisms to evade immunosurveillance. Although the development of immunotherapy is promising, primary resistance may develop in some patients and these patients do not benefit from immunotherapy. In addition, acquired resistance that may occur in clinical progression in patients who respond to treatment may limit the success of immunotherapy. Among the resistance mechanisms are tumor-specific pathways that lead to reduced function and infiltration of immune cells in the tumor microenvironment (TME). New strategies envisioning combination therapies with chemotherapy, radiotherapy and new immunomodulatory agents to prevent and overcome the onset of resistance are fairly promising. In this review, it is aimed to examine immunotherapeutic approaches (Immune Checkpoint Inhibitors (ICI), Lymphocyte Regulatory Cytokines, Cancer Vaccines, CAR T and T Cell Receptor (TCR), Costimulatory Receptors), current information about cancer immunotherapy, and patient responses to immunotherapy.

Keywords

cancer immunotherapy, immune checkpoint inhibitors, lymphocyte promoting cytokines, cancer vaccines, CAR T and T cell receptor

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