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Clin Cancer Res. 2014 Jul 15;20(14):3818-29. doi: 10.1158/1078-0432.CCR-13-3368. Epub 2014 Jun 10.

Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer.

Author information

1
Authors' Affiliations: Lineberger Comprehensive Cancer Center; Curriculum in Genetics and Molecular Biology; Departments of.
2
Authors' Affiliations: Lineberger Comprehensive Cancer Center; Medicine;
3
Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics;
4
Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics; Pathology and Laboratory Medicine; and cperou@med.unc.edu jonathan_serody@med.unc.edu.
5
Authors' Affiliations: Lineberger Comprehensive Cancer Center; Medicine; Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina cperou@med.unc.edu jonathan_serody@med.unc.edu.

Abstract

PURPOSE:

Lymphocytic infiltration of tumors predicts improved survival in patients with breast cancer. Previous studies have suggested that this survival benefit is confined predominantly to the basal-like subtype. Immune infiltration in ovarian tumors is also associated with improved prognosis. Currently, it is unclear what aspects of the immune response mediate this improved outcome.

EXPERIMENTAL DESIGN:

Using The Cancer Genome Atlas mRNA-seq data and a large microarray dataset, we evaluated adaptive immune gene expression by genomic subtype in breast and ovarian cancer. To investigate B-cells observed to be prognostic within specific subtypes, we developed methods to analyze B-cell population diversity and degree of somatic hypermutation (SHM) from B-cell receptor (BCR) sequences in mRNA-seq data.

RESULTS:

Improved metastasis-free/progression-free survival was correlated with B-cell gene expression signatures, which were restricted mainly to the basal-like and HER2-enriched breast cancer subtypes and the immunoreactive ovarian cancer subtype. Consistent with a restricted epitope-driven response, a subset of basal-like and HER2-enriched breast tumors and immunoreactive ovarian tumors showed high expression of a low-diversity population of BCR gene segments. More BCR segments showed improved prognosis with increased expression in basal-like breast tumors and immunoreactive ovarian tumors compared with other subtypes. Basal-like and HER2-enriched tumors exhibited more BCR sequence variants in regions consistent with SHM.

CONCLUSION:

Taken together, these data suggest the presence of a productive and potentially restricted antitumor B-cell response in basal-like breast and immunoreactive ovarian cancers. Immunomodulatory therapies that support B-cell responses may be a promising therapeutic approach to targeting these B-cell infiltrated tumors.

PMID:
24916698
PMCID:
PMC4102637
DOI:
10.1158/1078-0432.CCR-13-3368
[Indexed for MEDLINE]
Free PMC Article
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