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.

The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

“…E and F, ÃÃÃ , P 0.001 and ÃÃÃÃ , P 0.0001 4T1.2 versus 67NR (Mann-Whitney U test). cells in human breast tumors (41,42). Given that TAMs and neutrophils are the predominant immune cells in 4T1.2 primary tumors, we assessed whether any changes took place in peripheral blood monocytes and neutrophils during mammary tumor growth.…”

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

“…13 Accordingly, after exposure to neoadjuvant chemotherapy, approximately one-third of stage 2/ 3 breast cancers appeared highly infiltrated by cytotoxic T cells, with a concomitant reduction of B lymphocytes and Th2 cells. 14 Moreover, the relative proportions of macrophages and CD8 þ T cells predict the pathological responses to neoadjuvant anthracycline-based therapy and overall survival in locally advanced breast cancer. 15 As conventional chemotherapies can elicit tumor-specific T cell immunity, which then contribute to durably and negatively inflecting the tumor growth curve, we addressed the question whether anticancer therapies would also stimulate B cell-or Fc receptor (FcR)-dependent immune responses.…”

Repolarizing macrophages improves breast cancer therapy

“…In contrast, the infiltration of tumors by specific leukocyte cell subsets such as CD8 + and memory T-lymphocytes has been linked with favorable outcomes in different cancers, suggesting that immune engagement can limit cancer growth and spread [1]. Indeed, in breast cancers a low ratio of macrophages to CD8 + cells predicts survival suggesting a major role for macrophages in suppressing T cell activity against tumors [3]. The idea of enhancing T cell activity in tumors is supported by the success of clinical trials with immune checkpoint inhibitors (such as anti-CTLA4, anti-PD1, and anti-PDL1) in treating melanoma and lung cancers [4,5].…”