Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Heinrich-Pette-Institute, Leibniz-Institute for Experimental Virology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Int J Mol Sci. 2021 Apr 19;22(8):4213. doi: 10.3390/ijms22084213.
To fight cancer more efficiently with cell-based immunotherapy, more information about the cells of the immune system and their interaction with cancer cells in vivo is needed. Therefore paraffin wax embedded primary breast cancers from the syngeneic mouse WAP-T model and from xenografted tumors of breast, colon, melanoma, ovarian, neuroblastoma, pancreatic, prostate, and small cell lung cancer were investigated for the infiltration of immunocompetent cells by immunohistochemistry using antibodies against leukocyte markers. The following markers were used: CD45 as a pan-leukocyte marker, BSA-I as a dendritic cell marker, CD11b as an NK cell marker, and CD68 as a marker for macrophages. The labeled immune cells were attributed to the following locations: adjacent adipose tissue, tumor capsule, intra-tumoral septae, and cancer cells directly. In xenograft tumors, the highest score of CD45 and CD11b positive, NK, and dendritic cells were found in the adjacent adipose tissue, followed by lesser infiltration directly located at the cancer cells themselves. The detected numbers of CD45 positive cells differed between the tumor entities: few infiltrating cells in breast cancer, small cell lung cancer, neuroblastoma, a moderate infiltration in colon cancer, melanoma and ovarian cancer, strongest infiltration in prostate and pancreatic cancer. In the syngeneic tumors, the highest score of CD45 and CD11b positive, NK and dendritic cells were observed in the tumor capsule, followed by a lesser infiltration of the cancer tissue. Our findings argue for paying more attention to investigate how immune-competent cells can reach the tumor cells directly.
为了更有效地利用细胞免疫疗法对抗癌症,我们需要更多关于免疫系统细胞及其与体内癌细胞相互作用的信息。因此,我们使用针对白细胞标志物的抗体,通过免疫组织化学方法研究了来自同基因小鼠 WAP-T 模型和异种移植的乳腺癌、结肠癌、黑色素瘤、卵巢癌、神经母细胞瘤、胰腺癌、前列腺癌和小细胞肺癌的石蜡包埋原发性乳腺癌中免疫活性细胞的浸润情况。使用的标记物如下:CD45 作为一种泛白细胞标志物、BSA-I 作为树突状细胞标志物、CD11b 作为 NK 细胞标志物和 CD68 作为巨噬细胞标志物。标记的免疫细胞被归为以下位置:邻近的脂肪组织、肿瘤包膜、肿瘤内隔室和直接位于癌症细胞上。在异种移植肿瘤中,CD45 和 CD11b 阳性、NK 和树突状细胞的最高评分位于邻近的脂肪组织中,其次是位于癌症细胞本身的浸润程度较小。不同肿瘤实体中检测到的 CD45 阳性细胞数量不同:乳腺癌、小细胞肺癌、神经母细胞瘤中浸润细胞较少,结肠癌、黑色素瘤和卵巢癌中浸润细胞中等,前列腺癌和胰腺癌中浸润细胞最强。在同基因肿瘤中,CD45 和 CD11b 阳性、NK 和树突状细胞的最高评分位于肿瘤包膜中,其次是癌症组织的较小浸润。我们的研究结果表明,需要更多地关注研究免疫活性细胞如何直接到达肿瘤细胞。