title: Leukocyte composition of human breast cancer.
abstract: 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/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 provide an initial evaluation of differences in the immune microenvironment 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.
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Ruffell
authors.forename: Alfred
authors.initials: A
authors.lastname: Au
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Esserman
authors.forename: E Shelley
authors.initials: ES
authors.lastname: Hwang
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Coussens
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C067980:CD68 antigen, human; D000097382:CD68 Molecule