臺灣博碩士論文加值系統

在口咽癌中，免疫反應、致癌物、以及預後三者之間的關係至今尚未被釐清。此處，我們回溯性地檢閱了46位口咽癌病人的病理檢體，並使用p16來判定人類乳突病毒的狀態。促炎性細胞激素的免疫螢光染色顯示高表現量的interferon gamma (IFNγ; 屬於T helper 1; Th1)、低表現量的interleukin 4 (IL4; 屬於T helper 2; Th2)、低表現量的thymic stromal lymphopoietin (TSLP; 同樣屬於Th2)、和低表現量的transforming growth factor beta (TGFβ; 屬於T regulatory; Treg)對口咽癌來說是好的預後因子。p16陽性口咽癌，比起p16陰性口咽癌，有著更高的Th1促炎性細胞激素表現量、更低的Th2/Treg促炎性細胞激素表現量、以及更好的預後。若只看吸菸者，雖然p16陽性口咽癌吸菸者，比起p16陰性口咽癌吸菸者，仍然有著較弱的以Th2/Treg為主的促炎性細胞激素表現量，但兩組的預後卻都同樣不佳。而倘若只看p16陽性口咽癌病患，雖然p16陽性的非吸菸者，比起p16陽性的吸菸者，有著顯著更佳的預後，但兩組的免疫反應，卻均為以弱Th2/Treg為主。總結來說，高Th1和低Th2/Treg促炎性細胞激素與口咽癌較佳的預後有正相關。在口咽癌中，人類乳突病毒可能跟Th1免疫反應的提升、Th2/Treg免疫反應的降低、以及好的預後有正相關；而吸菸則可能跟Th2/Treg免疫反應提升、Th1免疫反應的降低、以及不好的預後有正相關。吸菸對口咽癌免疫偏向的影響可能小於人類乳突病毒，然而吸菸對口咽癌預後的影響卻可能大於人類乳突病毒，此代表除了免疫調節機制以外，其他環境因子及基因多型性等因素對於口咽癌預後的影響尚待更進一步釐清。

In oropharyngeal squamous cell carcinoma (OPSCC), the relationships between immune responses, carcinogens, and prognoses are not clarified yet. Here, we retrospectively reviewed the pathology samples of 46 OPSCC patients, and used p16 to determine their human papillomavirus (HPV) status. The immunofluorescence staining of proinflammatory cytokines showed that high interferon gamma (IFNγ; T helper 1; Th1), low interleukin 4 (IL4; T helper 2; Th2), low thymic stromal lymphopoietin (TSLP; Th2), and low transforming growth factor beta (TGFβ; T regulatory; Treg) expressions were good prognostic factors for OPSCC. p16-positive OPSCC showed higher Th1, lower Th2/Treg proinflammatory cytokine expressions, and a better prognosis than p16-negative OPSCC. In smokers alone, although p16-positive OPSCC smokers showed weaker Th2/Treg predominant cytokine expressions than p16-negative OPSCC smokers, the prognoses of both groups were equally poor. As for p16-positive OPSCC patients alone, p16-positive nonsmokers showed a significantly better prognosis than p16-positive smokers, but the immune responses of both groups were all weakly Th2/Treg predominant. Overall, higher Th1 and lower Th2/Treg proinflammatory cytokine expressions are associated with a better prognosis for OPSCC. HPV may be related to increased Th1, decreased Th2/Treg responses, and a good prognosis, while smoking may be related to increased Th2/Treg, decreased Th1 responses, and a poor prognosis in OPSCC. The impact of smoking on immune deviation may be weaker than that of HPV, but the impact of smoking on prognosis may be stronger than that of HPV in OPSCC. The further investigations on environmental or genetic factors in OPSCC are needed.

中文摘要...i
英文摘要...iii
誌謝...v
目錄...vi
表目錄...ix
圖目錄...x
縮寫對照表...xi
第一章 前言及文獻回顧...1
1.1 口咽癌與其致癌成因...1
1.2 p16與口咽癌人類乳突病毒狀態的判定...1
1.3 免疫反應與癌症的預後...3
1.4 致癌物與免疫反應的平衡...4
第二章 研究目的...6
第三章 實驗方法與材料...7
3.1 病人群體的選擇...7
3.2 p16免疫組織染色的流程與判定...7
3.3 促炎性細胞激素的免疫螢光染色...8
3.3.1 免疫螢光染色的流程...8
3.3.2 雙染一級抗體的選擇與搭配...9
3.3.3 免疫螢光強度的觀測與計算...10
3.4 統計分析...11
第四章 實驗結果...12
4.1 病人的臨床表徵與分組...12
4.2 口咽癌病理切片的染色...12
4.3 促炎性細胞激素的表現量...13
4.3.1 p16陽性和p16陰性組的比較...13
4.3.2 吸菸者p16陽性和p16陰性組的比較...14
4.3.3 p16陽性者吸菸和無吸菸組的比較...15
4.4 促炎性細胞激素之間的關聯性...15
4.5 p16、吸菸、和促炎性細胞激素的預後影響力...16
4.5.1 促炎性細胞激素表現量高低的切點...16
4.5.2 p16和吸菸的存活分析...16
4.5.3 促炎性細胞激素的存活分析...17
4.6 p16、吸菸、促炎性細胞激素、和預後之間的關係...17
第五章 討論...18
5.1 促炎性細胞激素、致癌物、與預後之間的關係...18
5.2 吸菸與口咽癌的免疫偏向...19
5.3 人類乳突病毒與口咽癌的免疫偏向...19
5.4 IL4與口咽癌細胞...20
5.5 人類乳突病毒陽性口咽癌的預後...21
5.6 吸菸與口咽癌預後的惡化...22
5.7 本研究的限制...22
第六章 結論...24
參考文獻...25
英文論文大綱...40

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