. 2018 Dec; 10(12):.
doi: 10.3390/cancers10120515.

Radiotherapy as a New Player in Immuno-Oncology

Shang-Jui Wang 1 Bruce Haffty 2 
  • PMID: 30558196
  •     142 References
  •     6 citations


Recent development in radiation biology has revealed potent immunogenic properties of radiotherapy in cancer treatments. However, antitumor immune effects of radiotherapy are limited by the concomitant induction of radiation-dependent immunosuppressive effects. In the growing era of immunotherapy, combining radiotherapy with immunomodulating agents has demonstrated enhancement of radiation-induced antitumor immune activation that correlated with improved treatment outcomes. Yet, how to optimally deliver combination therapy regarding dose-fractionation and timing of radiotherapy is largely unknown. Future prospective testing to fine-tune this promising combination of radiotherapy and immunotherapy is warranted.

Keywords: cancer; combination therapy; dose-fractionation; immunotherapy; radiation; radiotherapy; timing.

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Concomitant targeting of programmed death-1 (PD-1) and CD137 improves the efficacy of radiotherapy in a mouse model of human BRAFV600-mutant melanoma.
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Cancer Immunol Immunother, 2016 May 11; 65(6). PMID: 27160390    Free PMC article.
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy.
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PLoS One, 2016 Jun 10; 11(6). PMID: 27281029    Free PMC article.
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Cancer Immunol Immunother, 2016 Jul 05; 65(8). PMID: 27376889
Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.
Sebastian Theurich, Sacha I Rothschild, +16 authors, Max Schlaak.
Cancer Immunol Res, 2016 Jul 29; 4(9). PMID: 27466265
4-1BB Aptamer-Based Immunomodulation Enhances the Therapeutic Index of Radiation Therapy in Murine Tumor Models.
Ana Paula Benaduce, Randall Brenneman, +3 authors, Adrian Ishkanian.
Int J Radiat Oncol Biol Phys, 2016 Sep 07; 96(2). PMID: 27598810
Trial Watch: Immunotherapy plus radiation therapy for oncological indications.
Erika Vacchelli, Norma Bloy, +13 authors, Lorenzo Galluzzi.
Oncoimmunology, 2016 Oct 21; 5(9). PMID: 27757313    Free PMC article.
Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial.
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Eur J Cancer, 2016 Oct 21; 68. PMID: 27764686
Suppression of Type I IFN Signaling in Tumors Mediates Resistance to Anti-PD-1 Treatment That Can Be Overcome by Radiotherapy.
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Cancer Res, 2016 Nov 09; 77(4). PMID: 27821490    Free PMC article.
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The TLR7 agonist imiquimod induces anti-cancer effects via autophagic cell death and enhances anti-tumoral and systemic immunity during radiotherapy for melanoma.
Jeong Hyun Cho, Hyo-Ji Lee, +10 authors, Yu-Jin Jung.
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Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade.
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Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.
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Oncoimmunology, 2017 Jul 07; 6(6). PMID: 28680762    Free PMC article.
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J Immunother Cancer, 2017 Jul 19; 5(1). PMID: 28716061    Free PMC article.
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Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.
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N Engl J Med, 2017 Sep 09; 377(20). PMID: 28885881
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Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences.
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Immunol Rev, 2017 Oct 14; 280(1). PMID: 29027221
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TAMeless traitors: macrophages in cancer progression and metastasis.
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Martyna Śniegocka, Ewa Podgórska, +9 authors, Krystyna Urbańska.
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Radiation Followed by OX40 Stimulation Drives Local and Abscopal Antitumor Effects in an Anti-PD1-Resistant Lung Tumor Model.
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Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer.
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The Association of Radiation Dose-Fractionation and Immunotherapy Use With Overall Survival in Metastatic Melanoma Patients.
Shang-Jui Wang, Sachin R Jhawar, +7 authors, Sharad Goyal.
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Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma.
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Tumor Microenvironment as A "Game Changer" in Cancer Radiotherapy.
Magdalena Jarosz-Biej, Ryszard Smolarczyk, Tomasz Cichoń, Natalia Kułach.
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Efficacy of Local Treatments for Hepatocellular Carcinoma Involving the Inferior Vena Cava and/or Right Atrium.
Han Ah Lee, Chai Hong Rim.
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PI3Kδ/γ inhibitor BR101801 extrinsically potentiates effector CD8+ T cell-dependent antitumor immunity and abscopal effect after local irradiation.
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