In situ cytokine production by breast cancer tumor-infiltrating lymphocytes
In situ cytokine production by breast cancer tumor-infiltrating lymphocytes
复制标题
DOI：
10.1007/bf02305798
复制
发表时间：
1996-03-01
影响因子：
3.7
通讯作者：
Barth, RJ
中科院分区：
文献类型：
--
作者：
Camp, BJ;Dyhrman, ST;Barth, RJ
背景：尽管存在广泛的淋巴细胞浸润和特异性的抗肿瘤免疫识别，但人类乳腺癌仍在继续生长，因此人们对乳腺肿瘤浸润性淋巴细胞(TIL)的能力提出了质疑。乳腺TIL在体内的功能及其在抑制抗肿瘤免疫反应中的可能作用在很大程度上尚不清楚。方法：用免疫组织化学方法检测89例乳腺癌和14例乳腺良性病变中淋巴细胞产生的细胞因子。结果：大多数乳腺肿瘤和良性病变标本中存在T细胞浸润，抗CD3抗体染色揭示了这些T细胞的存在。IL-245%、IL-4 36%、肿瘤坏死因子-α28%、转化生长因子-β1 20%、IL-10 11%、干扰素-γ4%、粒-巨噬细胞集落刺激因子3%。乳腺癌患者TIL产生的IL-2、IL-4和转化生长因子-β(1)水平高于良性乳腺病变(P<；0.005)。肿瘤样本中产生IL-2、IL-4、转化生长因子-β(1)和肿瘤坏死因子-α的淋巴细胞显著多于干扰素-γ和粒-巨噬细胞集落刺激因子(p<；每个比较0.002)。在44%的标本中，淋巴细胞产生了一种或多种潜在的免疫抑制细胞因子-IL-4、IL-10或转化生长因子-β(1)，未发现特定细胞因子的淋巴细胞产生与无病生存期(中位随访43个月)之间的显著相关性。结论：免疫组织化学技术可用于检测保存组织中TIL的细胞因子分泌。干扰素-γ和粒-巨噬细胞集落刺激因子分泌的相对缺乏，而不是IL-2的缺乏，可能解释了为什么乳腺癌的抗肿瘤免疫反应受到了损害。
Background: Human breast cancers progressively grow despite the presence of extensive lymphocytic infiltration and specific antitumor immune recognition, thereby calling into question the competency of breast tumor-infiltrating lymphocytes (TIL). The function of breast TILs in vivo and their possible role in the suppression of an antitumor immune response are largely unknown.Methods: The cytokines produced in situ by lymphocytes in 89 boast carcinomas and 14 benign breast lesions were assessed using immunohistochemistry.Results: The majority of tumor and benign breast samples contained T-cell infiltrates, which were disclosed using an anti-CD3 antibody stain. The percentage of tumor samples in which greater than or equal to 3% of the lymphocytes were producing cytokines was as follows: interleukin (IL)-2 45%, IL-4 36%, tumor necrosis factor-alpha (TNF-alpha) 28%, transforming growth factor-beta 1 (TGF-beta(1)) 20%, IL-10 11%, interferon-gamma (IFN-gamma) 4%, and granulocyte-macrophage colony-stimulating factor (GM-CSF) 3%. Production of IL-2, IL-4, and TGF-beta(1) by TILs in breast cancers exceeded that detected in benign breast lesions (p < 0.005). Significantly more tumor samples contained lymphocytes producing IL-2, IL-4, TGF-beta(1), and TNF-alpha than IFN-gamma and GM-CSF (p < 0.002 for each comparison). One or more of the potentially immunoinhibitory cytokines - IL-4, IL-10, or TGF-beta(1) - were produced by lymphocytes in 44% of the specimens, No significant associations were seen between lymphocyte production of a particular cytokine and disease-free survival (median follow-up 43 months).Conclusions: Immunohistochemical techniques can be used to detect cytokine secretion by TILs in preserved tissue. The relative lack of secretion of IFN-gamma and GM-CSF, rather than a deficiency of IL-2, may explain why the antitumor immune response to breast cancer is impaired.