ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Induced Tumor Heterogeneity Reveals Factors Informing Radiation and Immunotherapy Combinations.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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
7 citing papers in PubMed, 14 citations in OpenAlex.
- The untapped potential of radiation and immunotherapy for hormone receptor-positive breast cancer.NPJ breast cancer · 2025Review
- Hypoxic Memory Mediates Prolonged Tumor-Intrinsic Type I Interferon Suppression to Promote Breast Cancer Progression.Cancer research · 2024Article
- Ultrafast power doppler ultrasound enables longitudinal tracking of vascular changes that correlate with immune response after radiotherapy.Theranostics · 2024Article
- Simultaneous selection of nanobodies for accessible epitopes on immune cells in the tumor microenvironment.Nature communications · 2023Article
- The immunogenic radiation and new players in immunotherapy and targeted therapy for head and neck cancer.Frontiers in oral health · 2023Review
- Mechanistic rationales for combining immunotherapy with radiotherapy.Frontiers in immunology · 2023Review
- Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
purposeTo investigate how induced tumor heterogeneity influences immune responses to radiotherapy with different proportions of mixed immune-responsive and unresponsive tumor cells in a triple-negative breast cancer model. It is hypothesized that studying the immune environment of mixed tumors and responses to radiotherapy could nominate immune active therapies to enhance immune responses after radiotherapy. EXPERIMENTAL
designEvaluate efficacy and immune responses generated by radiotherapy in tumors with different proportions of immunologically responsive and unresponsive tumor cells. Then study the cellular responses and transcriptomic differences between the tumors to nominate immunotherapy combinations with radiotherapy and evaluate the combination.
resultsThe addition of the responsive cells to unresponsive tumors led to a greater than expected therapeutic response to radiotherapy with both innate and adaptive immune components. There was a distinct change in myeloid cells, greater inflammatory macrophage activity, and enhanced antigen presentation with responsive cells after radiotherapy. Because differences in matrix components, cell adhesion biology, and innate immune signaling correlated with myeloid cell response and phenotype, we hypothesized that radiotherapy combined with CD40 agonist antibody would sensitize unresponsive tumors. The combination therapy resulted in improved innate and adaptive immune response. Importantly, CD40 treatment increased tumor response to radiotherapy and protected against metastatic spread in a metastatic model.
conclusionsThese data combined with transcriptomics from human patients support radiotherapy and myeloid cell targeting for immunologically cold tumors. The established study model presents opportunities to investigate the complex overlapping biologic mechanisms that limit immunotherapy and to implement radiotherapy with different immunotherapy combinations.
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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.