Review
. 2021 Feb; 13(4):.
doi: 10.3390/cancers13040678.

Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

Adrien Procureur 1 Audrey Simonaggio 1 Jean-Emmanuel Bibault 2 Stéphane Oudard 1 Yann-Alexandre Vano 1 
Affiliations
  • PMID: 33567530
  •     87 References
  •     5 citations

Abstract

The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence suggests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI. Here, we will describe the biological and radiobiological rationale of the RT-induced ICD. We will then focus on the interest to combine RT and ICI, from bench to bedside, and summarize the clinical data existing with this combination. Finally, RT technical adaptations to optimize the ICD induction will be discussed.

Keywords: cancer treatment; combination therapy; immune checkpoint inhibitors; immunogenic cell death; radioimmunotherapy; radiotherapy.

Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species.
Michael F Jobling, Joni D Mott, +8 authors, Mary Helen Barcellos-Hoff.
Radiat Res, 2006 Dec 08; 166(6). PMID: 17149983
The intersection of radiotherapy and immunotherapy: mechanisms and clinical implications.
Michael Spiotto, Yang-Xin Fu, Ralph R Weichselbaum.
Sci Immunol, 2016 Dec 27; 1(3). PMID: 28018989    Free PMC article.
Radiotherapy-Mediated Immunomodulation and Anti-Tumor Abscopal Effect Combining Immune Checkpoint Blockade.
Xinrui Zhao, Chunlin Shao.
Cancers (Basel), 2020 Oct 01; 12(10). PMID: 32992835    Free PMC article.
Review.
Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.
Scott J Antonia, Augusto Villegas, +28 authors, PACIFIC Investigators.
N Engl J Med, 2017 Sep 09; 377(20). PMID: 28885881
Highly Cited.
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death.
Lorenzo Galluzzi, Ilio Vitale, +51 authors, Francesco M Marincola.
J Immunother Cancer, 2020 Mar 27; 8(1). PMID: 32209603    Free PMC article.
Review.
Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape.
Carl DeSelm, M Lia Palomba, +4 authors, Michel Sadelain.
Mol Ther, 2018 Nov 13; 26(11). PMID: 30415658    Free PMC article.
Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas.
Jennifer E Kim, Mira A Patel, +23 authors, Michael Lim.
Clin Cancer Res, 2016 Jul 01; 23(1). PMID: 27358487    Free PMC article.
Highly Cited.
Radiotherapy as a Backbone for Novel Concepts in Cancer Immunotherapy.
Julijan Kabiljo, Felix Harpain, Sebastian Carotta, Michael Bergmann.
Cancers (Basel), 2020 Jan 08; 12(1). PMID: 31905723    Free PMC article.
Review.
Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma.
Ajay V Maker, James C Yang, +11 authors, Steven A Rosenberg.
J Immunother, 2006 Jun 27; 29(4). PMID: 16799341    Free PMC article.
Absolute Lymphocyte Count Predicts Abscopal Responses and Outcomes in Patients Receiving Combined Immunotherapy and Radiation Therapy: Analysis of 3 Phase 1/2 Trials.
Dawei Chen, Vivek Verma, +3 authors, James W Welsh.
Int J Radiat Oncol Biol Phys, 2020 Feb 10; 108(1). PMID: 32036004
Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment.
Ana P Kiess, Jedd D Wolchok, +6 authors, Kathryn Beal.
Int J Radiat Oncol Biol Phys, 2015 Mar 11; 92(2). PMID: 25754629    Free PMC article.
Highly Cited.
Complete Local and Abscopal Responses from a Combination of Radiation and Nivolumab in Refractory Hodgkin's Lymphoma.
Qian Qin, Xinyu Nan, +9 authors, Swaminathan P Iyer.
Radiat Res, 2018 Jun 28; 190(3). PMID: 29949442    Free PMC article.
The antitumor immune response generated by fractionated radiation therapy may be limited by tumor cell adaptive resistance and can be circumvented by PD-L1 blockade.
S J Dovedi, T M Illidge.
Oncoimmunology, 2015 Jul 04; 4(7). PMID: 26140246    Free PMC article.
Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study.
Steven F Powell, Kathryn A Gold, +15 authors, William C Spanos.
J Clin Oncol, 2020 Jun 02; 38(21). PMID: 32479189    Free PMC article.
Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial.
Salma K Jabbour, Abigail T Berman, +9 authors, Jyoti Malhotra.
JAMA Oncol, 2020 Feb 23; 6(6). PMID: 32077891    Free PMC article.
Radiation and immunotherapy: a synergistic combination.
Anusha Kalbasi, Carl H June, Naomi Haas, Neha Vapiwala.
J Clin Invest, 2013 Jul 19; 123(7). PMID: 23863633    Free PMC article.
Highly Cited.
TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity.
Claire Vanpouille-Box, Julie M Diamond, +5 authors, Sandra Demaria.
Cancer Res, 2015 Apr 11; 75(11). PMID: 25858148    Free PMC article.
Highly Cited.
Anti-PD-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma.
L Quéro, L Gilardin, +6 authors, P Brice.
Cancer Radiother, 2019 Feb 09; 23(2). PMID: 30733172
Immunogenic cell death in cancer therapy: Present and emerging inducers.
Jingyi Zhou, Gangyang Wang, +3 authors, Zhengdong Cai.
J Cell Mol Med, 2019 Jun 19; 23(8). PMID: 31210425    Free PMC article.
Highly Cited. Review.
Radiotherapy and immunotherapy: a beneficial liaison?
Ralph R Weichselbaum, Hua Liang, Liufu Deng, Yang-Xin Fu.
Nat Rev Clin Oncol, 2017 Jan 18; 14(6). PMID: 28094262
Highly Cited. Review.
Radiation as an immunological adjuvant: current evidence on dose and fractionation.
Sandra Demaria, Silvia C Formenti.
Front Oncol, 2012 Nov 01; 2. PMID: 23112958    Free PMC article.
Highly Cited.
Whole body irradiation; radiobiology or medicine?
R H MOLE.
Br J Radiol, 1953 May 01; 26(305). PMID: 13042090
Highly Cited.
Toxicity in combination immune checkpoint inhibitor and radiation therapy: A systematic review and meta-analysis.
Congzhou M Sha, Eric J Lehrer, +4 authors, Nicholas G Zaorsky.
Radiother Oncol, 2020 Jul 28; 151. PMID: 32717359
Systematic Review.
The molecular machinery of regulated cell death.
Daolin Tang, Rui Kang, +2 authors, Guido Kroemer.
Cell Res, 2019 Apr 06; 29(5). PMID: 30948788    Free PMC article.
Highly Cited. Review.
STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors.
Liufu Deng, Hua Liang, +12 authors, Ralph R Weichselbaum.
Immunity, 2014 Dec 18; 41(5). PMID: 25517616    Free PMC article.
Highly Cited.
Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1.
Cecilia Roux, Soode Moghadas Jafari, +14 authors, Chiara Gorrini.
Proc Natl Acad Sci U S A, 2019 Feb 17; 116(10). PMID: 30770442    Free PMC article.
TGFβ Blockade Enhances Radiotherapy Abscopal Efficacy Effects in Combination with Anti-PD1 and Anti-CD137 Immunostimulatory Monoclonal Antibodies.
María E Rodríguez-Ruiz, Inmaculada Rodríguez, +12 authors, Ignacio Melero.
Mol Cancer Ther, 2019 Jan 27; 18(3). PMID: 30683810
Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma.
Christopher A Barker, Michael A Postow, +5 authors, Jedd D Wolchok.
Cancer Immunol Res, 2014 Apr 30; 1(2). PMID: 24777500    Free PMC article.
Review.
Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming.
María E Rodriguez-Ruiz, Inmaculada Rodriguez, +13 authors, Ignacio Melero.
Cancer Res, 2016 Aug 24; 76(20). PMID: 27550452
Highly Cited.
Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC.
Jhanelle E Gray, Augusto Villegas, +17 authors, Scott J Antonia.
J Thorac Oncol, 2019 Oct 18; 15(2). PMID: 31622733    Free PMC article.
Relationship between pneumonitis induced by immune checkpoint inhibitors and the underlying parenchymal status: a retrospective study.
Chiara Pozzessere, Hasna Bouchaab, +7 authors, Catherine Beigelman-Aubry.
ERJ Open Res, 2020 Mar 24; 6(1). PMID: 32201690    Free PMC article.
Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies.
Inge Verbrugge, Jim Hagekyriakou, +8 authors, Nicole M Haynes.
Cancer Res, 2012 May 10; 72(13). PMID: 22570253
Highly Cited.
Pembrolizumab After Completion of Locally Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer: A Phase 2 Trial.
Joshua M Bauml, Rosemarie Mick, +11 authors, Corey J Langer.
JAMA Oncol, 2019 Jul 12; 5(9). PMID: 31294762    Free PMC article.
Highly Cited.
Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery.
Jack M Qian, James B Yu, Harriet M Kluger, Veronica L S Chiang.
Cancer, 2016 Jun 11; 122(19). PMID: 27285122    Free PMC article.
Highly Cited.
Immunogenic cell death in cancer therapy.
Guido Kroemer, Lorenzo Galluzzi, Oliver Kepp, Laurence Zitvogel.
Annu Rev Immunol, 2012 Nov 20; 31. PMID: 23157435
Highly Cited. Review.
A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?
Raffaella Marconi, Silvia Strolin, Gianluca Bossi, Lidia Strigari.
PLoS One, 2017 Feb 22; 12(2). PMID: 28222111    Free PMC article.
A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma.
Susan M Hiniker, Sunil A Reddy, +6 authors, Susan J Knox.
Int J Radiat Oncol Biol Phys, 2016 Sep 30; 96(3). PMID: 27681753    Free PMC article.
Highly Cited.
Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?
Michael B Bernstein, Sunil Krishnan, James W Hodge, Joe Y Chang.
Nat Rev Clin Oncol, 2016 Mar 10; 13(8). PMID: 26951040    Free PMC article.
Highly Cited. Review.
Safety of combining radiotherapy with immune-checkpoint inhibition.
William L Hwang, Luke R G Pike, +2 authors, Jay S Loeffler.
Nat Rev Clin Oncol, 2018 Jun 07; 15(8). PMID: 29872177
Highly Cited. Review.
Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells.
Chad Tang, James W Welsh, +17 authors, David S Hong.
Clin Cancer Res, 2016 Nov 01; 23(6). PMID: 27649551    Free PMC article.
Highly Cited.
Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice.
Liufu Deng, Hua Liang, +4 authors, Yang-Xin Fu.
J Clin Invest, 2014 Jan 03; 124(2). PMID: 24382348    Free PMC article.
Highly Cited.
Combining radiotherapy and cancer immunotherapy: a paradigm shift.
Silvia C Formenti, Sandra Demaria.
J Natl Cancer Inst, 2013 Jan 08; 105(4). PMID: 23291374    Free PMC article.
Highly Cited. Review.
DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity.
Claire Vanpouille-Box, Amandine Alard, +7 authors, Sandra Demaria.
Nat Commun, 2017 Jun 10; 8. PMID: 28598415    Free PMC article.
Highly Cited.
Impact of immunotherapy among patients with melanoma brain metastases managed with radiotherapy.
William A Stokes, David C Binder, +4 authors, Sana D Karam.
J Neuroimmunol, 2017 Nov 21; 313. PMID: 29153603
Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody.
M Zahidunnabi Dewan, Ashley E Galloway, +4 authors, Sandra Demaria.
Clin Cancer Res, 2009 Aug 27; 15(17). PMID: 19706802    Free PMC article.
Highly Cited.
Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.
Scott J Antonia, Augusto Villegas, +31 authors, PACIFIC Investigators.
N Engl J Med, 2018 Oct 04; 379(24). PMID: 30280658
Highly Cited.
Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination.
Amélie Aboudaram, Anouchka Modesto, +8 authors, Nicolas Meyer.
Melanoma Res, 2017 Sep 01; 27(5). PMID: 28858075
Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial.
Encouse B Golden, Arpit Chhabra, +9 authors, Silvia C Formenti.
Lancet Oncol, 2015 Jun 23; 16(7). PMID: 26095785
Highly Cited.
GM-CSF and ipilimumab therapy in metastatic melanoma: Clinical outcomes and immunologic responses.
Serena S Kwek, James Kahn, +8 authors, Lynn E Spitler.
Oncoimmunology, 2016 May 04; 5(4). PMID: 27141383    Free PMC article.
A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179.
Greg A Durm, Salma K Jabbour, +15 authors, Nasser H Hanna.
Cancer, 2020 Jul 23; 126(19). PMID: 32697352
Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.
Lionel Apetoh, François Ghiringhelli, +25 authors, Laurence Zitvogel.
Nat Med, 2007 Aug 21; 13(9). PMID: 17704786
Highly Cited.
Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study.
Gilles R Dagenais, Darryl P Leong, +29 authors, Salim Yusuf.
Lancet, 2019 Sep 08; 395(10226). PMID: 31492501
Highly Cited.
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy.
Kristina H Young, Jason R Baird, +9 authors, Marka R Crittenden.
PLoS One, 2016 Jun 10; 11(6). PMID: 27281029    Free PMC article.
Highly Cited.
Elective Nodal Irradiation Attenuates the Combinatorial Efficacy of Stereotactic Radiation Therapy and Immunotherapy.
Ariel E Marciscano, Ali Ghasemzadeh, +18 authors, Charles G Drake.
Clin Cancer Res, 2018 Jun 15; 24(20). PMID: 29898992    Free PMC article.
Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated.
Sandra Demaria, Bruce Ng, +4 authors, Silvia C Formenti.
Int J Radiat Oncol Biol Phys, 2004 Feb 18; 58(3). PMID: 14967443
Highly Cited.
Combined radiotherapy with nivolumab for extracranial metastatic malignant melanoma.
Tetsuya Komatsu, Kenta Konishi, +2 authors, Katsumasa Nakamura.
Jpn J Radiol, 2018 Sep 13; 36(12). PMID: 30206802
Optimising efficacy and reducing toxicity of anticancer radioimmunotherapy.
Eric Deutsch, Cyrus Chargari, Lorenzo Galluzzi, Guido Kroemer.
Lancet Oncol, 2019 Aug 01; 20(8). PMID: 31364597
Review.
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer.
Christina Twyman-Saint Victor, Andrew J Rech, +22 authors, Andy J Minn.
Nature, 2015 Mar 11; 520(7547). PMID: 25754329    Free PMC article.
Highly Cited.
A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma.
Michael A Postow, Susan J Knox, +22 authors, Christopher A Barker.
Clin Cancer Res, 2020 Mar 25; 26(13). PMID: 32205463    Free PMC article.
TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo.
Fanny Bouquet, Anupama Pal, +8 authors, Mary Helen Barcellos-Hoff.
Clin Cancer Res, 2011 Oct 27; 17(21). PMID: 22028490    Free PMC article.
Immune Priming of the Tumor Microenvironment by Radiation.
Wen Jiang, Charles K Chan, +2 authors, Stephen M Hahn.
Trends Cancer, 2017 Jul 26; 2(11). PMID: 28741502
Review.
Phase 1 study of stereotactic body radiotherapy and interleukin-2--tumor and immunological responses.
Steven K Seung, Brendan D Curti, +8 authors, Walter J Urba.
Sci Transl Med, 2012 Jun 08; 4(137). PMID: 22674552
Highly Cited.
Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial.
Eugene D Kwon, Charles G Drake, +24 authors, CA184-043 Investigators.
Lancet Oncol, 2014 May 17; 15(7). PMID: 24831977    Free PMC article.
Highly Cited.
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.
Narek Shaverdian, Aaron E Lisberg, +5 authors, Percy Lee.
Lancet Oncol, 2017 May 30; 18(7). PMID: 28551359    Free PMC article.
Highly Cited.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Chimeric antigen receptor T-cell therapy - assessment and management of toxicities.
Sattva S Neelapu, Sudhakar Tummala, +16 authors, Elizabeth J Shpall.
Nat Rev Clin Oncol, 2017 Sep 20; 15(1). PMID: 28925994    Free PMC article.
Highly Cited. Review.
Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade.
Simon J Dovedi, Amy L Adlard, +11 authors, Tim M Illidge.
Cancer Res, 2014 Oct 03; 74(19). PMID: 25274032
Highly Cited.
Combination of T-cell therapy and trigger of inflammation induces remodeling of the vasculature and tumor eradication.
Ruth Ganss, Eduard Ryschich, +2 authors, Günter J Hämmerling.
Cancer Res, 2002 Mar 13; 62(5). PMID: 11888921
Highly Cited.
Lost in Translation: Deciphering the Mechanism of Action of Anti-human CTLA-4.
Sergio A Quezada, Karl S Peggs.
Clin Cancer Res, 2018 Oct 07; 25(4). PMID: 30291135
Integrative Analysis Identifies a Novel AXL-PI3 Kinase-PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer.
Heath D Skinner, Uma Giri, +15 authors, John V Heymach.
Clin Cancer Res, 2017 May 10; 23(11). PMID: 28476872    Free PMC article.
Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors.
Jonathan M Pitt, Marie Vétizou, +8 authors, Laurence Zitvogel.
Immunity, 2016 Jun 23; 44(6). PMID: 27332730
Highly Cited. Review.
Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics.
Sayuri Miyauchi, Sangwoo S Kim, +6 authors, Andrew B Sharabi.
Clin Cancer Res, 2019 Mar 01; 25(14). PMID: 30814108    Free PMC article.
Review.
Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy.
K A Ahmed, D G Stallworth, +7 authors, G T Gibney.
Ann Oncol, 2015 Dec 30; 27(3). PMID: 26712903
Highly Cited.
Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation.
Lisa Deloch, Anja Derer, +3 authors, Udo S Gaipl.
Front Oncol, 2016 Jul 06; 6. PMID: 27379203    Free PMC article.
Highly Cited. Review.
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Lorenzo Galluzzi, Ilio Vitale, +166 authors, Guido Kroemer.
Cell Death Differ, 2018 Jan 25; 25(3). PMID: 29362479    Free PMC article.
Highly Cited. Review.
Radiation enhances regulatory T cell representation.
Evelyn L Kachikwu, Keisuke S Iwamoto, +5 authors, Dörthe Schaue.
Int J Radiat Oncol Biol Phys, 2010 Nov 26; 81(4). PMID: 21093169    Free PMC article.
Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival.
Jonathan P S Knisely, James B Yu, +3 authors, Veronica L S Chiang.
J Neurosurg, 2012 Jun 19; 117(2). PMID: 22702482    Free PMC article.
Highly Cited.
NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2020.
David S Ettinger, Douglas E Wood, +34 authors, Miranda Hughes.
J Natl Compr Canc Netw, 2019 Dec 06; 17(12). PMID: 31805526
Highly Cited.
Potential and unsolved problems of anti-PD-1/PD-L1 therapy combined with radiotherapy.
Yiyi Cao, Wenbo Li, ZhengJie Wang, Hua Pang.
Tumori, 2020 Aug 01; 107(4). PMID: 32734832
Review.
Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines.
James J Kobie, Rita S Wu, +6 authors, Emmanuel T Akporiaye.
Cancer Res, 2003 Apr 19; 63(8). PMID: 12702574
Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy.
Eric A Reits, James W Hodge, +14 authors, Jacques J Neefjes.
J Exp Med, 2006 Apr 26; 203(5). PMID: 16636135    Free PMC article.
Highly Cited.
Is the Combination of Immunotherapy and Radiotherapy in Non-small Cell Lung Cancer a Feasible and Effective Approach?
Mathieu Spaas, Yolande Lievens.
Front Med (Lausanne), 2019 Dec 04; 6. PMID: 31788476    Free PMC article.
Review.
Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor.
Amit A Lugade, James P Moran, +3 authors, Edith M Lord.
J Immunol, 2005 Jun 10; 174(12). PMID: 15944250
Highly Cited.
PD-1 Restrains Radiotherapy-Induced Abscopal Effect.
Sean S Park, Haidong Dong, +7 authors, Eugene D Kwon.
Cancer Immunol Res, 2015 Feb 24; 3(6). PMID: 25701325    Free PMC article.
Highly Cited.
Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases.
Charlee Nardin, Christine Mateus, +5 authors, Frederic Dhermain.
Melanoma Res, 2018 Jan 23; 28(2). PMID: 29356789
A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors.
Bhanu Prasad Venkatesulu, Supriya Mallick, Steven H Lin, Sunil Krishnan.
Crit Rev Oncol Hematol, 2018 Feb 28; 123. PMID: 29482778
Highly Cited. Systematic Review.
Maximizing tumor immunity with fractionated radiation.
Dörthe Schaue, Josephine A Ratikan, Keisuke S Iwamoto, William H McBride.
Int J Radiat Oncol Biol Phys, 2012 Jan 03; 83(4). PMID: 22208977    Free PMC article.
Highly Cited.
Immunotherapy in Treating EGFR-Mutant Lung Cancer: Current Challenges and New Strategies.
Kenneth K W To, Winnie Fong, William C S Cho.
Front Oncol, 2021 Jun 12; 11. PMID: 34113560    Free PMC article.
Review.
Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts.
Dietrich Averbeck, Claire Rodriguez-Lafrasse.
Int J Mol Sci, 2021 Oct 24; 22(20). PMID: 34681703    Free PMC article.
Review.
Narrative review of emerging roles for AKT-mTOR signaling in cancer radioimmunotherapy.
Changxian Shen, Yuqi He, +4 authors, Zhengfu He.
Ann Transl Med, 2021 Nov 19; 9(20). PMID: 34790802    Free PMC article.
Review.
Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice.
Jinguo Zhang, Shuaikang Pan, +5 authors, Xinghua Han.
Front Immunol, 2022 Jan 25; 12. PMID: 35069604    Free PMC article.
Review.
Combination of Anti-PD-1 Antibody, Anlotinib and Pegaspargase "Sandwich" With Radiotherapy in Localized Natural Killer/T Cell Lymphoma.
Peng Sun, Yu Wang, +7 authors, Zhi-Ming Li.
Front Immunol, 2022 Mar 04; 13. PMID: 35237257    Free PMC article.