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Title of Journal: Breast Cancer Res Treat

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Abbravation: Breast Cancer Research and Treatment

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Kluwer Academic Publishers-Plenum Publishers

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1573-7217

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Focused antibody response in plasma cellinfiltrat

Authors: Y Wang F Ylera M Boston S G Kang J L Kutok A J P KleinSzanto R P Junghans
Publish Date: 2007/03/28
Volume: 104, Issue: 2, Pages: 129-144
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Abstract

Breast tumors with prominent plasma cell PC infiltrates often have a more favorable natural course that may plausibly be mediated by antitumor activity of the elicited antibodies These breast tumorassociated PCs are typically IgG dominant in contrast to normal breast PCs which are mainly IgA It is our hypothesis that this PC infiltration represents a host immune response that is driven by one or more tumor antigens Previously we and others showed that medullary carcinoma MC had a focused repertoire and features suggestive of a protein antigen driven response Infrequently nonMC not otherwise specified NOS breast tumors may exhibit heavy PC infiltrations also of IgG isotype In this first characterization of this favorable prognosis NOS subgroup IgG heavy chain Hc and light chain Lc variable V regions from three PCinfiltrated NOS tumors were randomly cloned and sequenced We found biased V gene usage by the infiltrating PCs and somatic hypermutation in the rearranged Ig Hc and Lc V regions that were compatible with antigenic selection of the progenitor B cells The antibody response of NOS infiltrated breast cancer is repertoirefocused with 13–68 of isolates being clonally reiterated in the samples Each NOS patient used distinct Hc VDJ and Lc VJ rearrangements with her own immune response “footprint” but the overall pattern of gene usage followed that typical of exogenous antigeninduced immune responses The data are consistent with the hypothesis that PC infiltrates infrequently arising in NOS tumors as previously inferred for MC are in response to one or more breast cancerassociated protein tumor antigensWe gratefully acknowledge Dr Louis Weiner for availing to this study the excellent resources of the Fox Chase Cancer Center Tumor Bank Facility We also thank Dr A Ebralidze and Dr Q Ma for technical advice This work was supported by grants to R P J from the National Cancer Institute/NIH and the Massachusetts Department of Public Health

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