Breast carcinomas are often infiltrated by inflammatory cells, particularly macrophages and T lymphocytes, but the significance of these cells remains unclear. One possible role of these inflammatory cells is that they represent a cell-mediated immune response against the carcinoma. CD8(+) lymphocytes are a known crucial component of cell-mediated immunity. The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8(+) cytotoxic lymphocytes in breast cancer. Tumor-infiltrating CD8(+) lymphocytes were assessed by immunohistochemical staining of tissue microarray cores from 1,334 unselected breast tumors from patients with long-term follow-up. The number of CD8(+) T cells was counted in tumor nests (intratumoral), in stroma adjacent to tumor cells, and in stroma distant to tumor cells, and their relationship with clinical outcome was determined. The total number of CD8(+) cells was positively correlated with tumor grade (r(s) = 0.20; P < .001) and inversely correlated with patient's age at diagnosis, estrogen receptor-alpha (ER-α), and progesterone receptor (PgR) expression (Mann-Whitney U test, P < .001). The total patient cohort was randomly divided into two separate training and validation sets before performing univariate survival analysis. Total number and distant stromal CD8(+) lymphocytes were associated with better patient survival (P = .041 and P < .001, respectively) in the training set. In multivariate analysis, total CD8(+) T-cell count was an independent prognostic factor in both training and validation sets. These results suggest that tumor-infiltrating CD8(+) T lymphocytes have antitumor activity as judged by their favorable effect on patients' survival and could potentially be exploited in the treatment of breast cancer.

Macrophages are heterogeneous with different subsets having different functions. The present study suggests that overall macrophage numbers are not related to prognosis in breast cancer. However, further studies are needed to investigate the potential role of different subsets of macrophages.

Although the favourable role of T lymphocyte populations in different tumour types is established, that of B cells is still a matter of debate and needs further clarification. The presence of tumour-infiltrating B cells may represent an antibody response against breast tumour antigens. We used immunohistochemistry to investigate the density and localisation of B lymphocytes infiltrating 1470 breast tumours and to identify any prognostic significance and relationship to various clinicopathological factors. Higher numbers of CD20(+) cells were found in the stroma away from the carcinoma (mean 12 cells) compared with either intratumoural or adjacent stromal compartments (mean 1 cell). The majority of tumours showed a diffuse pattern of B cells rather than aggregates. There was a positive correlation between higher numbers of total CD20(+) B cells and higher tumour grade (r (s) = 0.20, P < 0.001), ER and PgR negativity (P < 0.001), and basal phenotype (P < 0.001) subclass. In univariate survival analysis, higher total number of infiltrating CD20(+) cells, irrespective of location, was associated with significantly better BCSS (P = 0.037) and longer DFI (P = 0.001). In multivariate analysis, total CD20(+) B cell count (HR = 0.75, 95% CI = 0.58-0.96 for BCSS and HR = 0.72, 95% CI = 0.58-0.89, for DFI), tumour size, nodal stage, grade, vascular invasion, HER-2 status, and total CD8(+) T cell count were independently associated with outcome. This suggests that humoral immunity, in addition to the cell mediated immunity, may be important in breast cancer. This should be considered in breast cancer immunotherapy and vaccine strategies.

Abstract:Introduction Studies in mice have that shown thymic-derived CD4+ CD25+

The metastasis of cancer is a complex and life-threatening process that is only partially understood. Immune suppressive cells are recognized as important contributors to tumour progression and may also promote the development and growth of tumour metastases. Specifically, regulatory T cells (Tregs) have been found to promote primary tumour progression, and emerging pre-clinical data suggests that Tregs may promote metastasis and metastatic tumour growth. While the precise role that Tregs play in metastatic progression is understudied, recent findings have indicated that by suppressing innate and adaptive anti-tumour immunity, Tregs may shield tumour cells from immune detection, and thereby allow tumour cells to survive, proliferate and acquire characteristics that facilitate dissemination. This review will highlight our current understanding of Tregs in metastasis, including an overview of pre-clinical findings and discussion of clinical data regarding Tregs and therapeutic outcome. Evolving strategies to directly ablate Tregs or to inhibit their function will also be discussed. Improving our understanding of how Tregs may influence tumour metastasis may lead to novel treatments for metastatic cancer.

Lymphocytic infiltration is often seen in breast cancer and has been suggested as a marker of host anti-tumor response but its importance in prognosis remains controversial. Our recent study demonstrated an association between tumor-infiltrating CD8+ T lymphocytes in invasive breast cancer and better prognosis.

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