Identification of Immune Cell Components in Breast Tissues by a Multiparametric Flow Cytometry Approach

CANCERS(2022)

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摘要
Simple Summary The tumor microenvironment in breast cancer plays important roles in tumor development and treatment response, giving important information critical for disease management. Today, an analysis of the tumor microenvironment is included in routine histopathologic reporting for practical clinical application. This manuscript aimed to deepen the study of the tumor microenvironment, analyzing the immune cells in breast tumoral and benign pathologies. Indeed, using a deep immunophenotyping approach by flow cytometry, we have studied the immune cells at the level of breast tissues, identifying different immunophenotyping that could be useful in the diagnosis and follow up of breast pathologies. As possible targets are continually being discovered in the tumor microenvironment, a future approach to breast cancer diagnosis and therapy could likely combine cancer cell elimination and tumor microenvironment modulation. Immune cell components are able to infiltrate tumor tissues, and different reports described the presence of infiltrating immune cells (TILs) in several types of solid tumors, including breast cancer. The primary immune cell component cells are reported as a lymphocyte population mainly comprising the cytotoxic (CD8+) T cells, with varying proportions of helper (CD4+) T cells and CD19+ B cells, and rarely NK cells. In clinical practice, an expert pathologist commonly detects TILs areas in hematoxylin and eosin (H&E)-stained histological slides via light microscopy. Moreover, other more in-depth approaches could be used to better define the immunological component associated with tumor tissues. Using a multiparametric flow cytometry approach, we have studied the immune cells obtained from breast tumor tissues compared to benign breast pathologies. A detailed evaluation of immune cell components was performed on 15 and 14 biopsies obtained from breast cancer and fibroadenoma subjects, respectively. The percentage of tumor-infiltrating T lymphocytes was significantly higher in breast cancer patients compared to patients with fibroadenoma. Infiltrating helper T lymphocytes were increased in the case of malignant breast lesions, while cytotoxic T lymphocytes disclosed an opposite trend. In addition, our data suggest that the synergistic effect of the presence/activation of NK cells and NKT cells, in line with the data in the literature, determines the dampening of the immune response. Moreover, the lymphocyte-to-monocyte ratio was calculated and was completely altered in patients with breast cancer. Our approach could be a potent prognostic factor to be used in diagnostic/therapeutic purposes for the improvement of breast cancer patients' management.
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tumor microenvironment, TILs, breast cancer, deep flow cytometry
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