乳癌是世界上女性常見的癌症類型且造成死亡的第二大主因，因此找到有效治療乳癌的方法是很重要的。除了手術、化療、放射線療法和標靶治療外，免疫療法也是具有潛力治療癌症的方法，像是阻斷免疫檢查點程序性死亡受體-1 (programmed cell death protein-1, PD-1)和程序性死亡配體-1 (programmed cell death ligand-1, PD-L1)的交互作用。介白素20 (IL-20)是屬於IL-10家族中一種促發炎的細胞激素。它透過兩種類型接受器的複合體來執行其生物功能，包括IL-20R1/IL-20R2或IL-22R1/IL-20R2。先前，我們發現IL-20的表現量與乳癌病患的臨床結果有相關性，且抗IL-20單株抗體(7E)能夠抑制乳癌的生長。此外我們也發現IL-20能夠去調控胰臟癌細胞PD-L1的表現量。所以在這項研究中，我們旨在探討乳癌中IL-20與PD-L1間的關係，並建立乳癌原位癌動物模型來探討7E合併抗PD-1單株抗體治療是否具有較佳的效果。在細胞實驗中，我們發現IL-20不僅誘導乳癌細胞PD-L1的表達，亦可上調促纖維化因子、促發炎因子以及與血管新生相關因子的表現，甚至與癌症相關成纖維母細胞的發展具有關聯性。而在動物實驗中，我們則發現在合併藥物治療(combination therapy)的組別中，其腫瘤體積和腫瘤重量相比於IgG、anti-PD-1抗體以及7E的組別都來得較小且輕。另外腫瘤當中PD-L1、TGF-β、VEGF-A和一些促發炎細胞激素的基因表現量在合併藥物治療的組別中也被下調。綜合以上的結果，我們結論IL-20參與在乳癌細胞PD-L1的調控，並且在乳癌的動物模型中發現以抗PD-1單株抗體與7E單株抗體兩者合併藥物治療具有較好的治療效果。

Breast cancer is the second leading cause of death among women in the world. In addition to surgery or other therapies, immunotherapy has been promising therapeutics to treat cancer, such as blocking binding immune checkpoint programmed cell death ligand -1 (PD-L1) to programmed cell death protein-1 (PD-1). Interleukin-20 (IL-20) is a proinflammatory cytokine that belongs to IL-10 family. It performs the biological functions through two types of receptor complex, either IL-20R1/IL-20R2 or IL 22R1/IL-20R2. Previously, we found that IL-20 expression was correlated with clinical outcomes of patients with breast cancer. Moreover, IL-20 could regulate PD-L1 expression on pancreatic cancer cells. Thus, in this study, we aimed to investigate the relationship between IL-20 and PD-L1 in breast cancer and establish orthotopic animal model to study whether combination of 7E and anti-PD-1 antibody treatment might have better efficacy. IL-20 not only induced PD-L1 expression but also up-regulated profibrogenic factors, proinflammatory cytokines and angiogenesis factors in breast cancer cell in vitro. Also, IL-20 may be involved in the development of CAFs. In vivo, We found that tumor volume and tumor weight were decreased in combination treatment group compared to IgG, anti-PD-1 antibody and 7 E group. Furthermore, PD-L1, TGF-β, VEGF-A and some proinflammatory cytokines gene expressions in tumor were downregulated by combination therapy. In conclusion, we discovered that IL-20 was involved in regulating breast cancer PD-L1 expression, and combination therapy had a better therapeutic effect in breast cancer model.

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