免疫檢查點抑制劑在癌症治療的發展與應用

Application of Immune Checkpoint Inhibitor in Cancer Treatment

黃國埕(Kuo-Cheng Huang)

《腫瘤護理雜誌》 18卷1期 (2018/06) Pp. 13-27

https://doi.org/10.3966/168395442018061801002

摘要

近幾年來蓬勃發展的免疫治療，為人類抗癌的戰爭帶來了一個嶄新的契機，其中免疫檢查點抑制劑已在多個臨床試驗中被證明它對不同癌症，包括非小細胞肺癌、大腸直腸癌、腎臟及泌尿道癌、頭頸癌、黑色素癌、胃癌、肝細胞癌和淋巴癌等的療效。目前的免疫檢查點抑制劑（immune checkpoint inhibitor），主要作用在CTLA-4和PD-1這兩個受體及PD-L1配體上，藉由恢復T細胞的活化，以加強人體對抗腫瘤的免疫反應，以達到腫瘤治療效果。相較於傳統的化學治療，免疫療法的副作用較為輕微。但是當病人免疫力被加強後，如果去傷害自身的組織器官，會造成類似自體免疫疾病的臨床表徵，產生所謂免疫治療的相關副作用。此類副作用可能影響人類所有器官，其中又以腸胃道、內分泌腺體、皮膚及肝臟發生率為最高。在治療期間甚至治療停止後，需持續監控病人異常的症狀，嚴重副作用發生時，可能會需要停止免疫治療用藥，同時併用全身性的類固醇治療。由於免疫治療費用昂貴，且非每位病人皆會有療效，故未來很重要的工作便是找出適當的預測因子，篩選適合的病人接受治療。而將來免疫治療能否取代現行的標準治療，治療的先後順序或能否協同治療以達最大治療效果，則有賴更多的臨床試驗來回答這些問題。

並列摘要

The rapid development of immunotherapy in recent years has brought new hope for human beings in defeating the cancer. Among the various immunotherapy agents, immune checkpoint inhibitors have demonstrated their effectiveness in treating different types of metastatic cancer such as non-small cell lung cancer, colorectal cancer, renal cell and genitourinary cancer, head and neck cancer, malignant melanoma, etc. Immune checkpoint inhibitors activate the function of T-cells by targeting CTLA-4 and PD-1 receptors and ligand PD-L1, thereby, enhancing human immune response to kill cancer cells. In comparison with chemotherapy, the side effects of immunotherapy may be minor. Nonetheless, activation of immune system can result in self-attack on normal organs which leads to a wide range of systemic symptoms and signs, the so-called immune-related adverse events. Gastrointestinal tract, endocrine system, skin and liver are particularly the most commonly involved sites. It is crucial to closely monitor patients' responses and abnormal symptoms. Steroid therapy or discontinuation of immunotherapy may be considered when needed. It should be noted that not every patient responds to immunotherapy, and added to that the high cost of this novelty therapy, it is imperative to identify a reliable predictor to help determine which patient can get clinical benefit from the therapy. Further clinical trials are needed to establish better integration of immunotherapy into current standard treatment.

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