Yamamura M, Modlin R L, Ohmen J D, Moy R L
Division of Dermatology, University of California, Los Angeles School of Medicine 90024.
J Clin Invest. 1993 Mar;91(3):1005-10. doi: 10.1172/JCI116256.
To characterize the nature of the local cytokine response to cancer, we chose to investigate cytokine patterns in biopsy specimens of basal cell carcinoma (BCC). We hypothesized that a distinct pattern of local cytokine production may be characteristic of BCC, a neoplasia of epidermis, in comparison to the pattern of seborrheic keratosis (SK), a benign growth of epidermis. We analyzed cytokine mRNAs in BCC versus SK by performing polymerase chain reaction on mRNA derived from biopsy specimens. The mRNAs encoding cytokines for IL-4, IL-5, IL-10, and granulocyte macrophage colony-stimulating factor were strongly expressed in BCC lesions and weakly expressed in SK lesions. Conversely, IL-2, IFN-gamma, and lymphotoxin mRNAs were strongly expressed in SK lesions and weakly expressed in BCC lesions. The response to malignancy, BCC, was typified by cytokines characteristic of murine TH2 cells. This cytokine pattern favors humoral immunity with concomitant immunosuppression of cell-mediated immune responses. In comparison, the response to the benign growth, SK, was typified by cytokines characteristic of murine TH1 cells that favor cell-mediated immune reactions. The findings of a distinct cytokine pattern in skin cancer provide a framework to develop strategies for immunologic intervention.
为了描述局部细胞因子对癌症反应的本质,我们选择研究基底细胞癌(BCC)活检标本中的细胞因子模式。我们假设,与脂溢性角化病(SK,一种表皮良性增生)的模式相比,局部细胞因子产生的独特模式可能是BCC(一种表皮肿瘤)的特征。我们通过对活检标本来源的mRNA进行聚合酶链反应,分析了BCC与SK中的细胞因子mRNA。编码白细胞介素-4、白细胞介素-5、白细胞介素-10和粒细胞巨噬细胞集落刺激因子的细胞因子mRNA在BCC病变中强烈表达,而在SK病变中弱表达。相反,白细胞介素-2、干扰素-γ和淋巴毒素mRNA在SK病变中强烈表达,而在BCC病变中弱表达。对恶性肿瘤BCC的反应以鼠TH2细胞特征性的细胞因子为典型。这种细胞因子模式有利于体液免疫,同时抑制细胞介导的免疫反应。相比之下,对良性增生SK的反应以鼠TH1细胞特征性的细胞因子为典型,这些细胞因子有利于细胞介导的免疫反应。皮肤癌中独特细胞因子模式的发现为制定免疫干预策略提供了一个框架。