ArticleOncotarget2016
Sublethal exposure to alpha radiation (223Ra dichloride) enhances various carcinomas' sensitivity to lysis by antigen-specific cytotoxic T lymphocytes through calreticulin-mediated immunogenic modulation.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 84 citations in OpenAlex.
- Radium-223 decreases PD-L1 expression in bone metastases: A study with [European journal of nuclear medicine and molecular imaging · 2026Article
- Potential Targets and Biomarkers of Radionuclide Therapy in Breast Cancer.Cancer innovation · 2026Review
- The role of the tumor microenvironment in mediating radiopharmaceutical therapy: bridging nuclear medicine and cancer immunotherapy.Military Medical Research · 2026Review
- Combination therapy of anEuropean journal of nuclear medicine and molecular imaging · 2026Article
- TIME for Endometrial Cancer: Advancements and Challenges in Therapeutic Targets for the Endometrial Cancer Tumor Immune Microenvironment.Cancer immunology research · 2025Review
- Targeted alpha therapy: a comprehensive analysis of the biological effects from "local-regional-systemic" dimensions.European journal of nuclear medicine and molecular imaging · 2025Review
- Radiation regulates the expression of HLA-I in esophageal squamous cell carcinoma through interferon-γ.Scientific reports · 2025Article
- Roles of the phagocytosis checkpoint in radiotherapy.Cell death & disease · 2025Review
- Effects of Targeted Radionuclide Therapy on Cancer Cells Beyond the Ablative Radiation Dose.International journal of molecular sciences · 2025Review
- MHC-I-Driven Antitumor Immunity Counterbalances Low Absorbed Doses of Radiopharmaceutical Therapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- The Tight Relationship Between the Tumoral Microenvironment and Radium-223.Biomedicines · 2025Review
- Current landscape and future directions of targeted-alpha-therapy for glioblastoma treatment.Theranostics · 2025Review
- Local radiation enhances systemic CAR T-cell efficacy by augmenting antigen crosspresentation and T-cell infiltration.Blood advances · 2024Article
- Characterization of Somatostatin Receptor 2 Gene Expression and Immune Landscape in Sinonasal Malignancies.Cancers · 2024Article
- Immune effects of α and β radionuclides in metastatic prostate cancer.Nature reviews. Urology · 2024Review
- Article
- Immunological effects of radiopharmaceutical therapy.Frontiers in nuclear medicine · 2024Review
- Radiopharmaceuticals heat anti-tumor immunity.Theranostics · 2023Review
- Developments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment.Pharmaceutics · 2022Review
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs). However, little is known about whether treatment with 223Ra can also induce such immunogenic modulation in tumor cells that survive irradiation. We examined these effects in vitro by exposing human prostate, breast, and lung carcinoma cells to sublethal doses of 223Ra. 223Ra significantly enhanced T cell-mediated lysis of each tumor type by CD8+ CTLs specific for MUC-1, brachyury, and CEA tumor antigens. Immunofluorescence analysis revealed that the increase in CTL killing was accompanied by augmented protein expression of MHC-I and calreticulin in each tumor type, molecules that are essential for efficient antigen presentation. Enhanced tumor-cell lysis was facilitated by calreticulin surface translocation following 223Ra exposure. The phenotypic changes observed after treatment appear to be mediated by induction of the endoplasmic reticulum stress response pathway. By rendering tumor cells more susceptible to T cell-mediated lysis, 223Ra may potentially be effective in combination with various immunotherapies, particularly cancer vaccines that are designed to generate and expand patients' endogenous antigen-specific T-cell populations against specific tumor antigens.
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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.