國立臺灣大學醫學院外科張金堅2006-07-262018-07-112006-07-262018-07-112004-07-31http://ntur.lib.ntu.edu.tw//handle/246246/24536在一些癌症中，腫瘤組織中有淋巴細胞的浸潤証實是預後較佳的徵候1-5。而這種現 象被認為是自體針對癌細胞所產生的特異性免疫反應，而非一般的發炎狀態。浸潤的淋 巴細胞絕大多數是帶有CD3+抗原的T 淋巴細胞，其中包含數目不等的CD4+及CD8+細 胞，NK 細胞只佔少數，B 淋巴細胞則不存在6-10。 在乳癌的研究則發現乳癌的期別與組織中浸潤淋巴細胞的多寡有關：癌細胞中的 浸潤淋巴細胞較正常組織中多，而且更常見。此外，CD4+/CD8 的比例愈高，腫瘤愈大， 淋巴腺轉移的機會也高11。在動物實驗中，TIL殺死癌細胞的能力高達LAK細胞的50-100 倍12，因此，腫瘤浸潤淋巴細胞 (TIL) 很有可能成為癌症誘發性免疫治療的明日之星。 本研究的第一年著重在了解浸潤淋巴細胞在腫瘤組織及正常乳腺的分佈情形，並與 血液中的分佈比較；第二年將會深入研究與腫瘤免疫調控相關的受體。 在浸潤淋巴球的分佈上，在23 位個案的完整分析中：腫瘤組織較正常組織為多( 4.15 ± 3.86 x 103 vs. 2.99 ± 3.78 x 103cell/mg, P=0.016)，與文獻報告一致。在比較免疫細胞在 腫瘤細胞及血液的分配比例方面，在腫瘤組織中，NK 細胞及B 細胞的比例遠低於血液 (P <0.001)；然而T 細胞（CD3+）的比例則較血液中為高(P <0.001)；若探究T 細胞中 CD4 及CD8 的分佈趨勢正好相反，腫瘤組織中的CD8+多，CD4+的比例則血液中較高， CD4+及CD8+的比值在兩造中正好相反，其所顯示的臨床意義有待進一步釐清，至於腫 瘤組織及正常組織的比較上，除了兩者在NK 細胞及B 細胞的比例相當外，T 細胞及其 中的CD4+及CD8+細胞的分佈趨勢與血液中的結果相似。Lymphoid infiltration in tumor tissues has been demonstrated a favorable sign for prognosis of hosts in several malignant tumors1-5. Therefore, lymphocytes’ infiltration is considered a result of tumor targeted, specific interactions rather than of an inflammatory response. Most of the infiltrating cells are CD3+ T cells with a variable number of CD4+ and CD8+. In most of the tumors, no B cells are found and natural killer cells constitute only a small minority of Tumor infiltrating lymphocytes (TIL)6-10. In human breast cancer , there was a significant reverse correlation between the intensity of the T-cell infiltration and the clinical stages. In general, lymphocytes are found more frequently and more abundantly in cancer than in its normal counterparts. Furthermore, it is observed an increased CD4+/CD8+ ratio correlated with tumor’s size and lymph node metastases 11. Studies in experimental animals have shown that the adoptive transfer of TIL is 50-100 times competent than LAK cell in mediating tumor regression12. Thus, TIL is a potentially promising candidate for adoptive immunotherapy. TIL from primary breast carcinomas can be propagated in large numbers in vitro with rIL2 while still retaining autologous tumor specificity and MHC-restricted CTL activity 13. In frist year of this project, we explored the distribution of immune cells in cancer , normal tissue and peripheral blood. The amount of mononuclear cells per mg of tissue in breast cancer was more than in its normal counterpart( 4.15 ± 3.86 x 103 vs. 2.99 ± 3.78 x 103cell/mg, P=0.016). Comparing the lymphocytes isolated from PBMCs and TILs, the median percentage on infiltrating natural killer (NK) cells and B cells was significantly lower in TILs than in PBMCs (P < 0.001 in NK cells and in B cells). We also found that the median percentage of CD3+ T cells in TILs was higher than that in PBMCs (P <0.001). High ratio of CD8+ T cell subpopulation was noted within gated autologous CD3+ TILs than PBMCs (63.1%±14.3%, vs. 33.3%±12.6%, P <0.001). Low ratio of CD4+ T cell subpopulation was noted within gated autologous CD3+ TILs than PBMCs (36.95%±14.29% vs. 66.68%±12.62%, P <0.001). The CD4+/CD8+ratio were significantly reversed in TILs (0.66±0.41 vs. 2.33±0.96, P <0.001), which was in accordance with our previous finding. The distribution of natural killer (NK) cells and B cells was similar in NILs and TILs. High ratio of CD8+ T cell (66.70%±14.19%, vs. 50.16%±14.02%, P =0.002) and low ratio of CD4+ T cell (33.30%±14.19% vs. 49.84%±14.01%, P=0.002) was also noted within gated autologous CD3+ TILs than NILs. The CD4/CD8 ratio were also significantly reversed in TILs (0.55±0.33 vs. 1.22±0.52, P <0.001), which was in accordance with our previous finding in cervical cancer.application/pdf131753 bytesapplication/pdfzh-TW國立臺灣大學醫學院外科乳癌腫瘤浸潤淋巴細胞(Tumor infiltrating lymphocyte, TIL)T 淋巴細胞Breast cancerTumor infiltrating lymphocyte (TIL)T lymphocyte[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/24536/1/922314B002279.pdf