Journal Article

DKFZ-2026-01109

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The contribution of rare germline variants to the immune landscape of breast cancer.

Rojas-Rodríguez, F. ; Canisius, S. ; Keeman, R. ; Bernstein, A. J. ; Hurson, A. N. ; Ahearn, T. U. ; Andrulis, I. L. ; Antoniou, A. C. ; Behrens, S.DKFZ* ; Białkowska, K. ; Blows, F. M. ; Bolla, M. K. ; Camp, N. J. ; Cessna, M. H. ; Chang-Claude, J.DKFZ* ; Chanock, S. J. ; Dennis, J. ; Devilee, P. ; Dunning, A. M. ; Gronwald, J. ; Hamann, U.DKFZ* ; Hollestelle, A. ; Hooning, M. J. ; Horlings, H. M. ; Jager, A. ; Jakubowska, A. ; Jones, B. ; Kaaks, R.DKFZ* ; Kok, M. ; Lissowska, J. ; Lubiński, J. ; Manoochehri, M.DKFZ* ; Miller, J. L. ; Muhammad, N. ; Mulligan, A. M. ; Obi, N. ; Rashid, M. U.DKFZ* ; Sinn, H.-P. ; van Deurzen, C. H. M. ; Wang, Q. ; Williams, J. A. ; Yang, X. R. ; Easton, D. F. ; Ali, H. R. ; García-Closas, M. ; Pharoah, P. D. P. ; Abubakar, M. ; Schmidt, M. K.

2026
BioMed Central London

Abstract: Many breast cancer predisposition genes are involved in DNA damage repair, leading to genome instability that can impact immunosurveillance, neoantigen formation, and the composition of the tumor immune microenvironment.Here, we explored associations between germline protein truncating variants (PTVs) in 34 (putative) breast cancer predisposition genes, of which 26 involved in DNA damage repair, with the abundance of four immune cell markers, i.e., CD8 + , FOXP3 + , CD20 + and CD163 + , across 7,969 invasive breast tumors of women of European ancestry.The most apparent associations were those of CD163, a marker of M2-like tumor-associated macrophages, with genes involved in double- and single-strand break DNA repair, and with the 12 known breast cancer predisposition genes combined. Specifically, DNA damage repair genes, BRCA1, BRCA2, PALB2, RAD51D, and MSH6 were associated with a 1.3 to twofold abundance of CD163-positive cells. Estrogen receptor status was found to mediate associations to a limited extent.Our findings support a role of rare pathogenic germline variants involved in DNA damage repair, and particularly those predisposing to breast cancer, in the immune landscape of breast tumors. These insights may help guide the development of immunomodulatory strategies for breast cancer prevention and treatment.

Keyword(s): Homologous recombination repair, macrophages ; Rare germline variants ; Tumor immune microenvironment

Note: epub

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Contributing Institute(s):

1. Epidemiologie von Krebs (C020)
2. Molekulargenetik des Mammakarzinoms (B072)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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