Leukocyte composition of human breast cancer

  • Ruffell B
  • Au A
  • Rugo H
 et al. 
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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 descrip-tions of leukocytic infiltrates, as well as evaluation of the functional state of leukocytes in BC stroma. To more fully evaluate this com-plexity, and to gain insight into immune responses after chemo-therapy (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 evalu-ated by polychromatic flow cytometry in combination with confocal immunofluorescence and immunohistochemical analysis of tissue sections. These studies revealed that activated T lymphocytes pre-dominate 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, ac-companied by an increased CD8/CD4 T-cell ratio and higher numbers of granzyme B-expressing cells, compared with tumors removed from patients treated primarily by surgery alone. These data pro-vide 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. inflammation | macrophage S everal subtypes of CD45-expressing leukocytes infiltrate breast cancer (BC), including CD4 + and CD8 + T cells, CD20 + B cells, and multiple myeloid-lineage cells including tumor-associated macrophages (TAMs) that are often identified by immunohistochemical (IHC) detection of CD68 (1). High lymphocyte infiltration is associated with increased survival in patients

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  • Brian Ruffell

  • Alfred Au

  • Hope S Rugo

  • Laura J Esserman

  • E Shelley Hwang

  • Lisa M Coussens

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