Barth R J, Camp B J, Martuscello T A, Dain B J, Memoli V A
Department of Surgery, Dartmouth-Hitchock Medical Center, Lebanon, NH 03756, USA.
Cancer. 1996 Sep 15;78(6):1168-78. doi: 10.1002/(SICI)1097-0142(19960915)78:6<1168::AID-CNCR2>3.0.CO;2-6.
The functional significance of cytokines expressed in situ by tumor cells and tumor infiltrating lymphocytes (TIL) in human colon carcinomas is largely unknown.
We assessed TIL expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), granulocyte-macrophage colony stimulating factor (GM-CSF), IL-10, and transforming growth factor-beta (TGF-beta), and tumor cell expression of IL-10 and TGF-beta in situ in 49 primary colon carcinomas and 20 metastases using immunohistochemistry.
The percentage of primary colon carcinoma samples in which > 20% of TIL expressed each cytokine was as follows: IL-4: 47%; TNF-alpha: 22%; TGF-beta: 10%; IFN-gamma: 6%; IL-2:2%; IL-10: 0%; and GM-CSF: 0%. Lymphocytes more commonly infiltrated colon carcinoma primaries than metastases, and TIL expression of IL-4 and TNF-alpha was more common in primary than metastastatic carcinomas. Expression of TNF-alpha by even a small proportion (> or = 3%) of the TIL in a colon carcinoma specimen was associated with better overall survival (P = 0.01) when compared with patients with little or no TIL TNF-alpha expression (5-year survival 82% vs. 47%). Expression of IL-4 by > or = 20% of colon carcinoma TIL was also associated with improved survival (P = 0.01; 5-year survival 87% vs. 50%). The expression of IL-10 or TGF-beta by colon carcinoma TIL or colon tumor cells themselves was not associated with impaired survival. Benign epithelial cells stained positively for IL-10 and TGF-beta more frequently than tumor cells (P < 0.001).
There are differences between the immune microenvironment of primary tumors and metastases. Although IL-10 is expressed by colon carcinoma cells and TIL, it is unlikely that it plays an important immunosuppressive role. TNF-alpha and IL-4 are commonly expressed by colon carcinoma TIL and both are associated with improved survival.
肿瘤细胞和肿瘤浸润淋巴细胞（TIL）原位表达的细胞因子在人类结肠癌中的功能意义很大程度上尚不清楚。
我们采用免疫组织化学方法评估了49例原发性结肠癌和20例转移癌中TIL白细胞介素-2（IL-2）、IL-4、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、IL-10和转化生长因子-β（TGF-β）的表达，以及肿瘤细胞原位IL-10和TGF-β的表达。
20%的TIL表达每种细胞因子的原发性结肠癌样本百分比分别如下：IL-4：47%；TNF-α：22%；TGF-β：10%；IFN-γ：6%；IL-2：2%；IL-10：0%；GM-CSF：0%。淋巴细胞浸润原发性结肠癌比转移癌更常见，且原发性癌中IL-4和TNF-α的TIL表达比转移性癌更常见。与TIL TNF-α表达很少或无表达的患者相比，结肠癌标本中即使一小部分（≥3%）TIL表达TNF-α也与更好的总生存期相关（P = 0.01）（5年生存率82%对47%）。≥20%的结肠癌TIL表达IL-4也与生存期改善相关（P = 0.01；5年生存率87%对50%）。结肠癌TIL或结肠肿瘤细胞自身表达IL-10或TGF-β与生存期受损无关。良性上皮细胞IL-10和TGF-β染色阳性比肿瘤细胞更频繁（P < 0.001）。
原发性肿瘤和转移瘤的免疫微环境存在差异。虽然IL-10由结肠癌细胞和TIL表达，但它不太可能发挥重要的免疫抑制作用。TNF-α和IL-4通常由结肠癌TIL表达，且两者均与生存期改善相关。
