ArticleCancer immunology research2015
CD4(+) T-Helper Type 1 Cytokines and Trastuzumab Facilitate CD8(+) T-cell Targeting of HER2/neu-Expressing Cancers.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 33 citations in OpenAlex.
- Determinants of Response to Sequential Pembrolizumab with Trastuzumab plus Platinum/5-FU in HER2-Positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- Neoadjuvant Immunotherapy in Hormone Receptor-Positive Breast Cancer: From Tumor Microenvironment Reprogramming to Combination Therapy Strategies.International journal of molecular sciences · 2025Review
- Bibliometric analysis of global research on breast cancer with HER2-low expression.Discover oncology · 2025Article
- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- Dual Functions of T Lymphocytes in Breast Carcinoma: From Immune Protection to Orchestrating Tumor Progression and Metastasis.Cancers · 2023Review
- Review
- Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment.Nature reviews. Drug discovery · 2022Review
- Breast Cancer Treatments: Updates and New Challenges.Journal of personalized medicine · 2021Review
- Differentiation and Regulation of TFrontiers in immunology · 2021Review
- HER2-Positive Breast Cancer Immunotherapy: A Focus on Vaccine Development.Archivum immunologiae et therapiae experimentalis · 2020Review
- T-helper 1-type cytokines induce apoptosis and loss of HER-family oncodriver expression in murine and human breast cancer cells.Oncotarget · 2019Article
- Sequential Anti-PD1 Therapy Following Dendritic Cell Vaccination Improves Survival in a HER2 Mammary Carcinoma Model and Identifies a Critical Role for CD4 T Cells in Mediating the Response.Frontiers in immunology · 2019Article
- Role of senescence induction in cancer treatment.World journal of clinical oncology · 2018Review
- Oncodriver inhibition and CD4Oncotarget · 2018Article
- Predicting the Efficacy of HER2-Targeted Therapies: A Look at the Host.Disease markers · 2017Review
- Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention.Frontiers in pharmacology · 2016Review
- Aptamer-Functionalized Nanoparticles as "Smart Bombs": The Unrealized Potential for Personalized Medicine and Targeted Cancer Treatment.Targeted oncology · 2015Review
- Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma.Scientific reports · 2015Article
- Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer.Breast cancer research : BCR · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Vaccination strategies incorporating the immunodominant HLA-A2-restricted HER2/neu-derived peptide 369-377 (HER2369-377) are increasingly utilized in HER2/neu-expressing cancer patients. The failure of postvaccination HER2369-377-specific CD8(+) T cells to recognize HLA-A2(pos)HER2/neu-expressing cells in vitro, however, has been attributed to impaired MHC class I/HLA-A2 presentation observed in HER2/neu-overexpressing tumors. We reconcile this controversy by demonstrating that HER2369-377 is directly recognized by high functional-avidity HER2369-377-specific CD8(+) T cells-either genetically modified to express a novel HER2369-377 TCR or sensitized using HER2369-377-pulsed type 1-polarized dendritic cells (DC1)-on class I-abundant HER2(low), but not class I-deficient HER2(high), cancer cells. Importantly, a critical cooperation between CD4(+) T-helper type-1 (Th1) cytokines IFNγ/TNFα and HER2/neu-targeted antibody trastuzumab is necessary to restore class I expression in HER2(high) cancers, thereby facilitating recognition and lysis of these cells by HER2369-377-specific CD8(+) T cells. Concomitant induction of PD-L1 on HER2/neu-expressing cells by IFNγ/TNF and trastuzumab, however, has minimal impact on DC1-sensitized HER2369-377-CD8(+) T-cell-mediated cytotoxicity. Although activation of EGFR and HER3 signaling significantly abrogates IFNγ/TNFα and trastuzumab-induced class I restoration, EGFR/HER3 receptor blockade rescues class I expression and ensuing HER2369-377-CD8(+) cytotoxicity of HER2/neu-expressing cells. Thus, combinations of CD4(+) Th1 immune interventions and multivalent targeting of HER family members may be required for optimal anti-HER2/neu CD8(+) T-cell-directed immunotherapy.
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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.