霍奇金氏淋巴瘤是一種惡性淋巴瘤，約有50%的患者和EB病毒感染有關。其在疾病初期治癒率較好，霍奇金氏淋巴瘤患者的五年存活率為86%。雖然霍奇金淋巴瘤治療效果良好，但初始化療方案中約有5％-10％的霍奇金氏淋巴瘤患者會復發，10%-30%的患者在初始治療後復發或變成難治性霍奇金淋巴瘤。因此，自體幹細胞移植（ASCT）是復發HL患者的治療標準，其治癒率約為50%。在某些研究指出，這些復發或難治性霍奇金淋巴瘤患者他們的基礎自噬量是增加的。而與EB病毒有關的其中一種潛伏膜蛋白LMP1可以促進細胞自噬，因此本研究想探討由LMP1所介導的細胞自噬在霍奇金氏淋巴瘤扮演什麼角色。我們分析了臨床數據，發現老年人、EB病毒與LMP1之間的相關性，進一步觀察整個亞型的霍奇金氏淋巴瘤整體對於性別、平均年齡、EB病毒、LMP1、細胞自噬標記LC3與霍奇金氏淋巴瘤3、4期患者的相關性。在細胞實驗我們利用L428-LMP1、KM-H2-EBV兩種霍奇金氏淋巴瘤細胞株進行實驗，主要利用細胞存活、死亡檢測及西方墨點法，來探討EB病毒或LMP1在霍奇金氏淋巴瘤中其細胞自噬的角色。我們發現LMP1轉染後會增強LC3的表現，當用細胞自噬抑制劑或臨床上常用來治療的化療藥物doxorubicin處理後，表現LMP1或EBV的霍奇金氏淋巴瘤細胞株會減弱與細胞自噬相關之細胞凋亡的表現量。綜合以上結果，我們霍奇金氏淋巴瘤的發展應與細胞自噬無關。此外，當LMP1或EBV存在於霍奇金氏淋巴瘤細胞株時，可部分地挽救由細胞自噬所引發的细胞凋亡。

Hodgkin's lymphoma (HL), a malignant lymphoma is associated with Epstein-Barr virus (EBV) infection in about 50% of patients. The initial stage of HL has good response for chemotherapy and the five-year survival rate of patients with HL is 86%. Although HL shows good response to treatment, approximately 5%-10% of HLs recur after initial chemotherapy and 10%-30% of HLs relapse or become refractory after remission from initial therapy. Thus, autologous stem cell transplant (ASCT) is the standard of care for patients with relapsed HLs with a cure rate of approximately 50%. In some studies, expression of basal autophagy signals in the patients with relapsed or refractory HLs is increased. Given that EBV-latent membrane protein 1 (LMP1) has been found to promote autophagy, this study was intended to explore the role of autophagy mediated by EBV or LMP1 in HL. We analyzed clinical data and found a correlation between the elderly, Epstein-Barr virus and LMP1.However, expression of the autophagy marker LC3 in HL was an uncommon event (15%) and independent of EBV status and clinical outcome. In cell experiments, we used L428-LMP1 and KMH2-EBV two HL cell lines to explore the role of EBV or LMP1 in HL survival in association with autophagy expression. We found that LMP1 transfection enhanced autophagy expression; when treatment with chloroquine or doxorubicin, LMP1 or EBV attenuated autophagy-associated apoptosis of HL cells. Therefore, expression of autophagy signals is irrelevant in HL cells whose survival is independent of autophagy activation. Furthermore, LMP1 or EBV may partially rescue autophagy-associated apoptosis of HL cells.

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