摘要
現時常採用放療、化療和手術切除治療癌症，但療效不穩、副作用大、復發率高、抵抗性強，燃眉之急極待解決。免疫治療是通過活化自體免疫功能來對抗腫瘤的療法，基於腫瘤免疫學和基因編輯技術的進步，免疫檢查點抑制劑和嵌合抗原受體T細胞成為新興癌症免疫治療，於血液腫瘤上取得顯著療效，但在擁有多種免疫規避機制的實體瘤上則未見成效，且費用高昂，副作用仍較大，未能被廣泛應用。研究發現實體瘤中存在大量M2表型巨噬細胞（macrophage, mφ），能促進腫瘤惡化和轉移，抑制抗腫瘤免疫反應，抵抗治療並使預後變差，但當mφ轉化為M1表型時則可促進腫瘤毒殺作用，顯示mφ是極具潛力的治療對象。本研究表述了近年腫瘤免疫學的理論和免疫治療的發展，重點描述和比較mφ免疫治療機制和療效，藉此找出新突破點。綜合來說，mφ免疫治療的關鍵在於促進M2轉為M1表型，並抑制腫瘤細胞抗吞噬作用。雖然大部份mφ免疫治療仍處於臨床試驗，但已於不同腫瘤患者上取得顯著療效，且耐受性良好，更能與低劑量傳統化療藥物和免疫檢查點抑制劑產生協同效應。未來應更深入探討治療的機制和靶向，設法篩選易感患者，並把療效局部化，即可發揮更大效益和減低副作用，增加多靶向合併治療的可能，更全面地抑制腫瘤生長相關的多種途徑。
並列摘要
Radiotherapy, chemotherapy, and surgical resection are currently used to treat cancer, but the efficacy is unstable, with adverse side effects, high recurrence rate, and strong resistance. Immunotherapy is a treatment that individual uses self body's own immune system to fight cancer. Based on advances in tumor immunology and gene editing techniques, immune checkpoint inhibitors and chimeric antigen receptor T cells have become emerging cancer immunotherapies and have achieved significant efficacies in hematologic malignancies. However, it has not been widely used since there was no obvious effect on solid tumors with multiple immune evasion mechanisms also the high cost and still large side effect. Studies have found that there are a large number of M2 endotype mφ (macrophage, mφ) in solid tumors, which can promote tumor progression and metastasis, inhibit anti-tumor immune responses, resist treatment, and worsen prognosis, but they also can promote tumors toxicity once mφ are transformed into the M1 endotype, indicating that mφ are potential therapeutic target. This study describes the recent developments in the theory of tumor immunology and the development of immunotherapy, focusing on the description and comparison of mφ immunotherapeutic mechanisms and efficacies, in order to identify new breakthroughs. In summary, the key to mφ immunotherapy is to promote the transformation of M2 to M1 endotype and inhibit tumor cell anti-phagocytosis axis. Although most of the mφ immunotherapies are still in clinical trials, some treatments have already achieved significant efficacy in patients with different tumors, well tolerated, and can produce synergistic effects with low-dose traditional chemotherapy drugs and immune checkpoint inhibitors. In the future, dig deeper into mechanisms and targeting of treatments, develop methods to screen susceptible patients, and localize the efficacy are needed to bring greater benefits and not only reduce side effects, but also increase the possibility of multi-target therapy used to more comprehensively suppress tumors which have a variety of pathways related to growth.
參考文獻
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