Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity.

Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Molecular mechanisms of this suppression remain elusive, however. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B7-H1, a member of the B7 family, on the cell surface. B7-H1 could be further upregulated by tumor environmental factors. Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B7-H1. Blockade of B7-H1 enhanced MDC-mediated T-cell activation and was accompanied by downregulation of T-cell interleukin (IL)-10 and upregulation of IL-2 and interferon (IFN)-gamma. T cells conditioned with the B7-H1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, upregulation of B7-H1 on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy.

Unusual cases of metastases to the breast. A report of 17 cases diagnosed by fine needle aspiration.

BACKGROUND: Although nonmammary tumors metastatic to the breast are relatively uncommon, a correct diagnosis is essential to appropriate management. Radiologically these lesions are single, round, discrete lesions without the spiculations of primary malignancies. Fine needle aspiration biopsy (FNAB) may provide a definitive diagnosis, thereby sparing patients unnecessary surgery. CASES: Seventeen cases of nonmammary malignancies diagnosed by fine needle aspiration of the breast were identified in the cytopathology files at three different institutions from 1989 to 1999. Three of the cases are of particular interest, including a mucoepidermoid carcinoma of salivary gland origin and a small cell undifferentiated carcinoma of rectal origin, neither of which has been reported in the literature previously. The third case was a male with a breast mass that was originally thought to be primary based on clinical, cytologic and immunocytochemical features but subsequently was determined to be a metastasis from the lung. CONCLUSION: Virtually any malignancy may metastasize to the breast. FNAB is the best approach to the diagnosis of tumors that either clinically or radiographically are not typical of primary breast tumors. Extramammary neoplasms metastatic to the breast may be definitively diagnosed by FNAB, resulting in the most appropriate as well as cost-effective patient management.