Abstract

Abstract Breast cancer is the most common invasive cancer in women in the United States and many other parts of the world. About 80% of all the breast cancers are Invasive Ductal Carcinomas (IDC). Breast cancers often show detectable lymphocytic infiltrates, and only about one-fourth of them contain moderate to heavy infiltration of B-cells and plasma cells. B cells are the effector cells of humoral immunity and can terminally differentiate into antibody secreting plasma cells. In the present study, we have analyzed the immunoglobulin variable genes of tumor-infiltrating plasma cells from IDC patients. This was done to determine the clonal character of the plasma cells and their possible role in the tumor immunity. Fresh malignant breast tumors were obtained following surgery, and their frozen sections were screened for the lymphocytic infiltration. The tumor samples from patients which showed good plasma cell-infiltration were used for this study. Both malignant breast tumors, A55 (estrogen receptor-positive 80%; progesterone receptor-positive >90%) and A91 (estrogen receptor positive 70%; progesterone receptor positive 90%), were categorized as invasive ductal carcinomas. Using a laser capture microdissection technique (PALM Microlaser Technologies AG, Bernried, Germany), single and small clusters of plasma cells in the tumors were collected. The tumor plasma cells were processed for human immunoglobulin variable gene analysis using appropriate RT-PCR primer sets for heavy and light chains. A set of B- cells from healthy volunteer blood was also run as a RT-PCR quality control. The analyses of variable regions (VHeavy and VLight) of immunoglobulin genes show a very limited number of plasma cell clones in both the tumors. These results indicate their origin from a possible B-cell germ center within the tumor. These plasma cells may be secreting antibodies relevant to the tumor antigens. In order to confirm this, we plan to clone these VH and VL genes and produce antibodies in vitro and examine their binding to the tumor from which they were derived. The work will be extended to study the effects of these antibodies on breast cancer cell proliferation. Citation Format: Anurag Shukla, Yu-Jing Sun, David Krag. Oligoclonal characterization of tumor-infiltrating plasma cells in breast cancer: Germ cell expansion and immunity . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4974. doi:10.1158/1538-7445.AM2013-4974

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