ArticleOncoimmunology
Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Microbiome and Response to Therapy in Triple Negative Breast Cancer: A Systematic Review.Oncology research · 2026Pooled it
- A Systematic Review of Immune Cell Roles in Breast Cancer Immunotherapy.Cancer reports (Hoboken, N.J.) · 2025Pooled it
- Review
- The promyelocytic leukemia PML protein coordinates immune evasion in triple-negative breast cancer via independent and converging mechanisms.Cell death and differentiation · 2026Article
- Landscape of T-cell bispecific antibodies in cancer therapy: therapeutic strategies, challenges and future prospection.Molecular cancer · 2026Review
- Podoplanin-defined tumour plasticity and CCR7-mediated lymphatic metastasis in triple-negative breast cancer.British journal of cancer · 2026Article
- Iron diminishes immunosuppressive macrophages and enhances anti-PD-1 immunotherapy in breast cancer models.Journal of experimental & clinical cancer research : CR · 2026Article
- APOBEC3B-driven mutations negatively regulated by P53 promote tumor progression and immunosuppressive microenvironment in prostate cancer.Molecular and cellular biochemistry · 2026Article
- Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.Nature biotechnology · 2025Article
- Breast Cancer Cell Lines AT-3 and E0771 Decrease Mechanical and Cold Sensitivity, Along With Oestrous Cycle and Inflammatory Marker Alterations, in Wild-Type C57BL/6J Female Mice.European journal of pain (London, England) · 2025Article
- Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer.Journal for immunotherapy of cancer · 2025Article
- Glutathione peroxidase 4 (GPX4) and obesity interact to impact tumor progression and treatment response in triple negative breast cancer.Cancer & metabolism · 2025Article
- Current insights and future directions of Li-Fraumeni syndrome.Discover oncology · 2024Review
- Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent "NoGlow" Mice.Cancer research communications · 2024Article
- Endogenous pAKT activity is associated with response to AKT inhibition alone and in combination with immune checkpoint inhibition in murine models of TNBC.Cancer letters · 2024Article
- Breaking Barriers: The Promise and Challenges of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer.Biomedicines · 2024Review
- Enniatin A inhibits the chaperone Hsp90 and unleashes the immune system against triple-negative breast cancer.iScience · 2023Article
- Dormant tumors circumvent tumor-specific adaptive immunity by establishing a Treg-dominated niche via DKK3.JCI insight · 2023Article
- Article
- Combinatorial blockade for cancer immunotherapy: targeting emerging immune checkpoint receptors.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB. While promising, these modest response rates highlight the need for mechanistic studies to understand how different ICBs function, how their combination impacts functionality and efficacy, as well as what immunologic parameters predict efficacy to different ICBs regimens in TNBC. To address these issues, we tested anti-PD1 and anti-CTLA4 in multiple models of TNBC and found that their combination profoundly enhanced the efficacy of either treatment alone. We demonstrate that this efficacy is due to anti-CTLA4-driven expansion of an individually unique T-cell receptor (TCR) repertoire whose functionality is enhanced by both intratumoral Treg suppression and anti-PD1 blockade of tumor expressed PDL1. Notably, the individuality of the TCR repertoire was observed regardless of whether the tumor cells expressed a nonself antigen (ovalbumin) or if tumor-specific transgenic T-cells were transferred prior to sequencing. However, responsiveness was strongly correlated with systemic measures of tumor-specific T-cell and B-cell responses, which along with systemic assessment of TCR expansion, may serve as the most useful predictors for clinical responsiveness in future clinical trials of TNBC utilizing anti-PD1/anti-CTLA4 ICB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.