癌症免疫療法用藥PD-1抑制劑在 皮膚癌治療上的新發現

Cancer Immunotherapeutic Drug PD-1 Inhibitor Targets Melanoma Cell-intrinsic PD-1 Receptor to Suppress Tumor Growth Likewise

利用阻斷Ｔ細胞免疫檢查點CTLA-4或PD-1之功能，進而活化腫瘤組織內T細胞行使毒殺癌細胞活性所開發而成的蛋白質抑制劑藥物，是近年來癌症治療上極為重要且有效用的一種免疫治療方法。目前相關的抑制劑在癌症治療上已取得可觀的成果，其中尤以PD-1抑制劑對於皮膚癌的臨床治療效果最為顯著，然而其詳細作用機制則尚未明朗。最新研究顯示，PD-1抑制劑除了先前所報導的能幫助免疫T細胞攻擊皮膚癌細胞以外，還能直接與較惡性的皮膚癌細胞作用，透過抑制細胞內mTOR的訊號途徑進而抑制皮膚癌細胞增生。該發現讓PD-1抑制劑作為抗癌藥物有了更令人期待的效果。

CTLA-4 (cytotoxic T-lymphocyte associated protein 4) and PD-1 (programmed cell death 1) are two dominant immune checkpoint proteins on activated T cells. Therapeutic antibodies that inhibit these two proteins, known as immune checkpoint blockade, are used as therapeutic drugs to enhance the cytotoxicity of activated T cells against tumor. Three of these therapeutic antibodies are approved by the U.S. FDA, and shown to be beneficial in treating some cancers particularly in melanoma of the skin. The latest results disclosed that among these treatments a PD-1 inhibitor has shown not only to promote the regression of melanoma via activated T cell, but also to suppress melanoma size via directly inhibition on PD-1 and mTOR pathway of the skin cancer cells. This discovery reveals a prominent clinical value of anti-PD-1 therapy.