{
  "abstract": "PARP inhibitors (PARPi) drive efficacy in BRCA-mutant breast cancer (BC) via DNA damage-induced synthetic lethality and immune activation, supporting their combination with immune checkpoint blockade. In the TALAVE study, patients with advanced BRCA-mutant or wild-type (WT) HER2-negative BC received talazoparib followed by talazoparib plus avelumab. Only BRCA-mutant BC responded clinically. Serial multi-omic profiling revealed BRCA-dependent tumor-immune remodeling, including sustained H2AX-pTBK1 signaling with increased CD8+ T cells, tumor cell depletion, and enrichment of CD163+ macrophages. In contrast, BRCA-WT tumors remained compact and immunosuppressed with reduced T cells after therapy. PD-1+ T cells localized to CD4+-rich neighborhoods and correlated with longer progression-free survival in BRCA-mutant tumors. However, PD-L1+ cells were rapidly depleted or confined to immune-excluded regions, spatially segregating them from PD-1+ T cells, impairing effective checkpoint blockade. These findings suggest limited benefit of PD-1/PD-L1 blockade in augmenting PARPi activity and highlight the need for alternative strategies to sustain PARPi-induced immunity.",
  "abstract_shown": true,
  "affiliations": [
    "Brigham and Women's Hospital"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "name": "F. Lynce"
    },
    {
      "name": "K. Shimada"
    },
    {
      "name": "C. Isaacs"
    },
    {
      "name": "X. Geng"
    },
    {
      "name": "E. T. Richardson"
    },
    {
      "name": "A. Nelson"
    },
    {
      "name": "C. Mainor"
    },
    {
      "name": "M. Wei"
    },
    {
      "name": "J. M. Collins"
    },
    {
      "name": "P. R. Pohlmann"
    },
    {
      "name": "A. L. Heeke"
    },
    {
      "name": "K. F. Zheng"
    },
    {
      "name": "M. Townsend"
    },
    {
      "name": "N. Swanson"
    },
    {
      "name": "L. M. Sloat"
    },
    {
      "name": "J. Staunton"
    },
    {
      "name": "S. J. Schnitt"
    },
    {
      "name": "H. Wang"
    },
    {
      "name": "J. S. Brugge"
    },
    {
      "name": "G. I. Shapiro"
    },
    {
      "affs": [
        0
      ],
      "name": "J. L. Guerriero"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/401x06raa2g9r.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.752386",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752386v1.full",
  "id": "401x06raa2g9r",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752386v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|PARP inhibition in cancer therapy"
    ]
  ],
  "openalex": "W7213543751",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752386v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/401x06raa2g9r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:02Z",
      "native_id": "10.64898/2026.09.17.752386",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752386v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "TALAVE in Breast Cancer: BRCA1/2 Mutation-Dependent Immune Remodeling after PARP Inhibition with Limited Checkpoint Engagement",
  "title_text": "TALAVE in Breast Cancer: BRCA1/2 Mutation-Dependent Immune Remodeling after PARP Inhibition with Limited Checkpoint Engagement",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:02Z",
  "url": "https://research.draconitic.com/paper/401x06raa2g9r",
  "venue": "bioRxiv",
  "versions": []
}