Peran Kunci cGAS dan Trex1 dalam Modulasi Respon Imun Terhadap Radiasi
Authors: Rafli Rhandyka , Harahap Wirsma Arif , Gondhowiardjo Soehartati , Ekaputra Andani 
Published: September 2024

Background: The immune response to tumors triggered by radiation is a complex phenomenon involving interactions between various immune system components and cellular molecules. The cGAS (Cyclic GMP-AMP Synthase) and Trex1 (Three-prime Repair Exonuclease 1) genes play important roles in detecting and responding to radiation-induced DNA damage, through the cGAS-STING pathway and the dsDNA degradation mechanism, respectively. This study discusses the critical role of cGAS and Trex1 in modulating the immune response to radiation.
Methods: This study is an observational literature review that summarizes meta-analysis studies, systematic observations, randomized clinical trials, observational studies, and case reports regarding the role of cGAS and Trex1 in radiation-induced immune responses. The search study was conducted on online databases published up to 2023.
Results: cGAS recognizes dsDNA in the cytosol and triggers an innate immune response through the production of cGAMP, which activates the adapter protein STING, causing the expression of proinflammatory cytokines. In contrast, Trex1 functions to eliminate DNA fragments, reducing excessive stimulation of the cGAS-STING pathway, which is important for avoiding autoimmune responses and increasing the efficacy of anti-tumor therapy. Research shows that radiation dose fractionation affects the activation and efficacy of this immune response, with certain doses and fractionation schemes increasing Trex1 expression and influencing the immune response to tumor cells which can have local and systemic impacts in the form of abscopal effects.
Conclusion: The interaction between the cGAS and Trex1 genes plays an important role in regulating the immune response to DNA damage induced by radiation. Through activation of the cGAS-STING pathway and modulation by Trex1, radiation therapy not only damages cancer cell DNA but also triggers an immune response that can enhance tumor amplification.

Latar belakang: Respon imun terhadap tumor yang terpicu oleh radiasi merupakan fenomena kompleks yang melibatkan interaksi antara berbagai komponen sistem imun dan molekul seluler. Gen cGAS (Cyclic GMP-AMP Synthase) dan Trex1 (Three-prime Repair Exonuclease 1) memainkan peranan kritis dalam mendeteksi dan merespon kerusakan DNA yang diinduksi oleh radiasi, melalui pathway cGAS-STING dan mekanisme degradasi dsDNA, masing-masing. Penelitian ini membahas mengenai peran kunci cGAS dan Trex1 dalam modulasi respon imun terhadap radiasi.
Metode: Studi ini adalah studi tinjauan pustaka yang memuat rangkuman studi meta analisis, tinjauan sistematis, uji klinis acak, studi observasional dan laporan kasus terkait peran cGAS dan Trex1 dalam respon imun terpicu radiasi. Pencarian studi dilakukan pada basis data online yang terpublikasi hingga tahun 2023.
Hasil: cGAS mengenali dsDNA di sitosol dan memicu respon imun innate melalui produksi cGAMP, yang mengaktifkan protein adaptor STING, menyebabkan ekspresi sitokin proinflamasi. Sebaliknya, Trex1 berfungsi untuk mengeliminasi fragmen DNA, mengurangi stimulasi berlebihan dari pathway cGAS-STING, yang penting untuk menghindari respon autoimun dan meningkatkan efikasi terapi anti-tumor. Penelitian menunjukkan bahwa fraksinasi dosis radiasi mempengaruhi aktivasi dan efikasi respon imun ini, dengan dosis dan skema fraksinasi tertentu meningkatkan ekspresi Trex1 dan mempengaruhi respon imun terhadap sel tumor yang bisa berdampak secara local maupun secara sistemik berupa abscopal effect.
Simpulan: Interaksi antara gen cGAS dan Trex1 memegang peran penting dalam mengatur respon imun terhadap kerusakan DNA yang diinduksi oleh radiasi. Melalui aktivasi jalur cGAS-STING dan modulasi oleh Trex1, terapi radiasi tidak hanya merusak DNA sel kanker tetapi juga memicu respon imun yang dapat memperkuat penghancuran tumor.