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Leukocyte composition of human breast cancer

机译:人乳腺癌的白细胞组成

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摘要

Retrospective clinical studies have used immune-based biomarkers, alone or in combination, to predict survival outcomes for women with breast cancer (BC); however, the limitations inherent to immunohistochemical analyses prevent comprehensive descriptions of leukocytic infiltrates, as well as evaluation of the functional state of leukocytes in BC stroma. To more fully evaluate this complexity, and to gain insight into immune responses after chemotherapy (CTX), we prospectively evaluated tumor and nonadjacent normal breast tissue from women with BC, who either had or had not received neoadjuvant CTX before surgery. Tissues were evaluated by polychromatic flow cytometry in combination with confocal immunofluorescence and immunohistochemical analysis of tissue sections. These studies revealed that activated T lymphocytes predominate in tumor tissue, whereas myeloid lineage cells are more prominant in "normal" breast tissue. Notably, residual tumors from an unselected group of BC patients treated with neoadjuvant CTX contained increased percentages of infiltrating myeloid cells, accompanied by an increased CD8/CD4T-cell ratioand highernumbers of granzyme B-expressing cells, compared with tumors removed from patients treated primarily by surgery alone. These data provide an initial evaluation of differences in the immune microenvi-ronment of BC compared with nonadjacent normal tissue and reveal the degree to which CTX may alter the complexity and presence of selective subsets of immune cells in tumors previously treated in the neoadjuvant setting.
机译:回顾性临床研究已单独或组合使用基于免疫的生物标志物来预测乳腺癌女性的生存结果。然而,免疫组织化学分析固有的局限性阻止了对白细胞浸润的全面描述以及对BC基质中白细胞功能状态的评估。为了更全面地评估这种复杂性,并深入了解化学疗法(CTX)后的免疫反应,我们前瞻性评估了来自BC妇女的肿瘤和非邻近的正常乳腺组织,这些妇女在手术前已经或未接受新辅助CTX。通过多色流式细胞术结合共聚焦免疫荧光和组织切片的免疫组织化学分析来评估组织。这些研究表明,活化的T淋巴细胞在肿瘤组织中占主导地位,而髓系谱系细胞在“正常”乳腺组织中更为突出。值得注意的是,与主要由经CTX治疗的患者切除的肿瘤相比,未经选择的新辅助CTX治疗的BC患者组的残留肿瘤含有增加的浸润性髓样细胞百分比,伴随着CD8 / CD4T细胞比率的增加和颗粒酶B表达细胞数量的增加。独自手术。这些数据提供了与不相邻正常组织相比BC免疫微环境差异的初步评估,并揭示了CTX可能改变先前在新辅助治疗中治疗的肿瘤中免疫细胞选择性亚群的复杂性和存在的程度。

著录项

  • 来源
  • 作者单位

    Department of Pathology, University of California, San Francisco, CA 94143;

    Department of Pathology, University of California, San Francisco, CA 94143,Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143;

    Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143,Departments of Medicine, University of California, San Francisco, CA 94115;

    Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143,Departments of Surgery, University of California, San Francisco, CA 94115;

    Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143,Departments of Surgery, University of California, San Francisco, CA 94115;

    Department of Pathology, University of California, San Francisco, CA 94143,Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    inflammation; macrophage;

    机译:炎;巨噬细胞;

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