ArticleThe Journal of clinical investigation2021
Radiotherapy-exposed CD8+ and CD4+ neoantigens enhance tumor control.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.
- Enhanced efficacy of lung cancer treatment with radiotherapy and immune checkpoint inhibitors without increased pneumonia risk: a systematic review and meta-analysis of randomized controlled trials.Frontiers in immunology · 2025Pooled it
- Synergies between radiotherapy and immunotherapy: a systematic review from mechanism to clinical application.Frontiers in immunology · 2025Pooled it
- Dynamic immune profiling predicts response to radiation plus anti-PD-1 therapy in oligometastatic renal cell carcinoma.Nature communications · 2026Trial
- Continuous Androgen Deprivation Therapy with or Without Metastasis-directed Therapy for Oligometastatic Prostate Cancer: The Multicenter Phase 2 Randomized EXTEND Trial.European urology · 2025Trial
- Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer.Journal for immunotherapy of cancer · 2025Trial
- A phase II randomized trial of individualized neoantigen peptide vaccine combined with unusual radiotherapy (iNATURE) in advanced solid tumors-GCOG0028.Frontiers in immunology · 2025Trial
- Review
- Combining Radiation Therapy and Tumor-Infiltrating Lymphocyte Therapy: Biological Rationale, Clinical Synergies, and Future Directions.Current oncology (Toronto, Ont.) · 2026Review
- Overcoming Drug Resistance by Paclitaxel Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Radiotherapy and immunotherapy in cancer treatment: mechanisms of clinical synergy.The Journal of clinical investigation · 2026Review
- Combining Radiation-Treated Tumor Vaccines With Mn-MOF Nanoadjuvants to Amplify Radiation Induced Anti-Tumor Immune Responses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Combining radiotherapy with CAR-T cell therapy for solid tumors: Challenges, mechanisms, and future directions.Precision radiation oncology · 2026Review
- The Double-Edged Sword: How Radiotherapy Shapes the Tumor Immune Microenvironment to Modulate Responses to Checkpoint Inhibitors.International journal of molecular sciences · 2026Review
- Evaluation of the abscopal-like effect of radioimmunotherapy on sentinel lymph nodes in H22 hepatocellular carcinoma via dynamic lymphography.BMC cancer · 2026Article
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- Review
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Heterologous prime-boost immunization of AAV-based neoantigen cancer vaccine induces anti-tumor immunity to inhibit tumor growth and relapse.Cancer immunology, immunotherapy : CII · 2026Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Neoantigens generated by somatic nonsynonymous mutations are key targets of tumor-specific T cells, but only a small number of mutations predicted to be immunogenic are presented by MHC molecules on cancer cells. Vaccination studies in mice and patients have shown that the majority of neoepitopes that elicit T cell responses fail to induce significant antitumor activity, for incompletely understood reasons. We report that radiotherapy upregulates the expression of genes containing immunogenic mutations in a poorly immunogenic mouse model of triple-negative breast cancer. Vaccination with neoepitopes encoded by these genes elicited CD8+ and CD4+ T cells that, whereas ineffective in preventing tumor growth, improved the therapeutic efficacy of radiotherapy. Mechanistically, neoantigen-specific CD8+ T cells preferentially killed irradiated tumor cells. Neoantigen-specific CD4+ T cells were required for the therapeutic efficacy of vaccination and acted by producing Th1 cytokines, killing irradiated tumor cells, and promoting epitope spread. Such a cytotoxic activity relied on the ability of radiation to upregulate class II MHC molecules as well as the death receptors FAS/CD95 and DR5 on the surface of tumor cells. These results provide proof-of-principle evidence that radiotherapy works in concert with neoantigen vaccination to improve tumor control.
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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.