Updates on radiotherapy-immunotherapy combinations: Proceedings of 6^th annual ImmunoRad conference

Fabiana Gregucci^{1

2}, Sheila Spada¹, Mary Helen Barcellos-Hoff³, Nina Bhardwaj^{4

5}, Charleen Chan Wah Hak⁶, Alba Fiorentino^{2

7}, Chandan Guha⁸, Monica L Guzman^{9

10}, Kevin Harrington¹¹, Fernanda G Herrera¹², Jamie Honeychurch¹³, Theodore Hong¹⁴, Lorea Iturri¹⁵, Elisabeth Jaffee¹⁶, Sana D Karam¹⁷, Simon R V Knott¹⁸, Constantinos Koumenis¹⁹, David Lyden²⁰, Ariel E Marciscano¹, Alan Melcher²¹, Michele Mondini^{22

23

24}, Anna Mondino²⁵, Zachary S Morris²⁶, Sean Pitroda²⁷, Sergio A Quezada²⁸, Laura Santambrogio^{1

10

29}, Stephen Shiao³⁰, John Stagg³¹, Irma Telarovic³², Robert Timmerman³³, Marie-Catherine Vozenin³⁴, Ralph Weichselbaum³⁵, James Welsh³⁶, Anna Wilkins³⁷, Chris Xu³⁸, Roberta Zappasodi^{39

40

41}, Weiping Zou⁴², Alexandre Bobard⁴³, Sandra Demaria^{1

44}, Lorenzo Galluzzi^{1

10

29}, Eric Deutsch^{22

23

24}, Silvia C Formenti^{1

10}

Affiliations

¹ Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.
² Department of Radiation Oncology, Miulli General Regional Hospital, Acquaviva delle Fonti, Bari, Italy.
³ Department of Radiation Oncology, School of Medicine, University of California, San Francisco, CA, USA.
⁴ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Translational Immunotherapy Team, The Institute of Cancer Research, London, UK.
⁷ Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy.
⁸ Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA.
⁹ Division of Hematology/Oncology, Department of Medicine, Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.
¹⁰ Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
¹¹ The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust, National Institute for Health Research Biomedical Research Centre, London, UK.
¹² Centre Hospitalier Universitaire Vaudois, University of Lausanne and Ludwig Institute for Cancer Research at the Agora Cancer Research Center, Lausanne, Switzerland.
¹³ Division of Cancer Sciences, University of Manchester, Manchester, UK.
¹⁴ Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁵ Institut Curie, Université PSL, CNRS UMR3347, INSERM U1021, Signalisation Radiobiologie et Cancer, Orsay, France.
¹⁶ Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
¹⁷ Department of Radiation Oncology, University of Colorado, Aurora, CO, USA.
¹⁸ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁹ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁰ Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
²¹ Division of Radiotherapy and Imaging, Institute of Cancer Research, London, UK.
²² Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
²³ Université of Paris-Saclay, Saclay, France.
²⁴ INSERM U1030, Radiothérapie Moléculaire et Innovation Thérapeutique, Villejuif, France.
²⁵ Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²⁶ Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²⁷ Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.
²⁸ Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
²⁹ Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA.
³⁰ Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³¹ Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, Faculty of Pharmacy, Montreal, Canada.
³² Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.
³³ Departments of Radiation Oncology and Neurosurgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
³⁴ Laboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
³⁵ Department of Radiation and Cellular Oncology, Ludwig Center for Metastases Research, University of Chicago, IL, USA.
³⁶ The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁷ Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom, Royal Marsden Hospital, Sutton, UK.
³⁸ School of Applied and Engineering Physics, Cornell University, Ithaca, NY, USA.
³⁹ Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
⁴⁰ Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
⁴¹ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
⁴² Departments of Surgery and Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁴³ Gustave Roussy Cancer Campus, Villejuif, France.
⁴⁴ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

PMID: 37363104
PMCID: PMC10286673
DOI: 10.1080/2162402X.2023.2222560

Review

Updates on radiotherapy-immunotherapy combinations: Proceedings of 6^th annual ImmunoRad conference

Fabiana Gregucci et al. Oncoimmunology. 2023.

. 2023 Jun 21;12(1):2222560.

doi: 10.1080/2162402X.2023.2222560. eCollection 2023.

Authors

Affiliations

¹ Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.
² Department of Radiation Oncology, Miulli General Regional Hospital, Acquaviva delle Fonti, Bari, Italy.
³ Department of Radiation Oncology, School of Medicine, University of California, San Francisco, CA, USA.
⁴ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Translational Immunotherapy Team, The Institute of Cancer Research, London, UK.
⁷ Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy.
⁸ Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA.
⁹ Division of Hematology/Oncology, Department of Medicine, Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.
¹⁰ Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
¹¹ The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust, National Institute for Health Research Biomedical Research Centre, London, UK.
¹² Centre Hospitalier Universitaire Vaudois, University of Lausanne and Ludwig Institute for Cancer Research at the Agora Cancer Research Center, Lausanne, Switzerland.
¹³ Division of Cancer Sciences, University of Manchester, Manchester, UK.
¹⁴ Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁵ Institut Curie, Université PSL, CNRS UMR3347, INSERM U1021, Signalisation Radiobiologie et Cancer, Orsay, France.
¹⁶ Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
¹⁷ Department of Radiation Oncology, University of Colorado, Aurora, CO, USA.
¹⁸ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁹ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁰ Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
²¹ Division of Radiotherapy and Imaging, Institute of Cancer Research, London, UK.
²² Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
²³ Université of Paris-Saclay, Saclay, France.
²⁴ INSERM U1030, Radiothérapie Moléculaire et Innovation Thérapeutique, Villejuif, France.
²⁵ Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²⁶ Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²⁷ Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.
²⁸ Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
²⁹ Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA.
³⁰ Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³¹ Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, Faculty of Pharmacy, Montreal, Canada.
³² Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.
³³ Departments of Radiation Oncology and Neurosurgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
³⁴ Laboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
³⁵ Department of Radiation and Cellular Oncology, Ludwig Center for Metastases Research, University of Chicago, IL, USA.
³⁶ The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁷ Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom, Royal Marsden Hospital, Sutton, UK.
³⁸ School of Applied and Engineering Physics, Cornell University, Ithaca, NY, USA.
³⁹ Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
⁴⁰ Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
⁴¹ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
⁴² Departments of Surgery and Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁴³ Gustave Roussy Cancer Campus, Villejuif, France.
⁴⁴ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

PMID: 37363104
PMCID: PMC10286673
DOI: 10.1080/2162402X.2023.2222560

Abstract

Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels. Here, we summarize the key concepts and findings presented at the Sixth Annual ImmunoRad conference.

Keywords: FLASH radiotherapy; dose and fractionation; immune checkpoint inhibitors; immunomodulators; lymph node sparing; tumor-associated macrophages.

PubMed Disclaimer

Conflict of interest statement

MHBH is or has have been a recipient of research grants paid to UCSF or in-kind resources from Roche-Genentech, Varian Medical Systems, Eli Lilly, Pathway Innovations and has received fees for consulting from EMD-Serono, Varian Medical Systems, Genentech, Pathway Innovation, Scholar Rock. KHhas Honoraria: Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Codiak Biosciences (Inst), F-Star Therapeutics (Inst), Inzen Therapeutics (Inst), Merck Serono (Inst), MSD (Inst), Oncolys Biopharma (Inst), Pfizer (Inst), Replimune (Inst), VacV Biotherapeutics (Inst); Consulting or Advisory Role: Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Inzen Therapeutics (Inst), Merck Serono (Inst), MSD (Inst), Oncolys BioPharma (Inst), Replimune (Inst); Speakers’ Bureau: BMS (Inst), Merck Serono (Inst), MSD (Inst); Research Funding: AstraZeneca (Inst), Boehringer Ingelheim (Inst), Merck Sharp & Dohme (Inst), Replimune (Inst). FGH received Grant or Research Support Companies from Accuray inc, Bioprotect, Bristol-Myers Squibb, Roche-ImFlame/ImCore, Nanobiotix, AstraZeneca, Debio Pharmaceuticals, Seagen, Eisai, MSD; Grant or Research Support Foundations from Prostate Cancer Foundation, San Salvatore Foundation; Investigator or Co-Investigator Clinical Trials in Bristol-Myers Squibb; Consultations: Johnson & Johnson; Academic Collaborations: EORTC chairman Gynecology Cancer Group, ESMO Scientific Committee member for drug development, ASTRO Scientific Committee Annual Meeting. TH has Consulting: Synthetic Biologics, Novocure, Boston Scientific, Inivata, Merck, GSK; Scientific Advisory Board: PanTher Therapeutics (Equity), Lustgarten; Research Funding (Clinical Trials): Taiho, AstraZeneca, BMS, GSK, IntraOp, Ipsen. EJ reports other support from Abmeta and Adventris, personal fees from Achilles, Dragonfly, Mestag, The Medical Home Group, and Surgtx, other support from Parker Institute, grants and other support from the Lustgarten Foundation, Genentech, BMS, and Break Through Cancer outside the submitted work. SDK receives clinical funding from AstraZeneca, Genentech, and Ionis; she also receives preclinical research funding from Roche. KS is founder and consultant for Faeth Therapeutics and Transomic Technologies. CK is the co-recipient of a Sponsored Research Agreement from Ion Beam Applications (IBA). AM is funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC IG 2018 Id.21763 and AIRC Programma di ricerca 5 per Mille 2019 Id.22737). MM declare grants from Boehringer Ingelheim, AC Biosciences and MSD outside the submitted work. ZSM has Scientific Advisory Board roles and equity options with Archeus Technologies and Seneca Therapeutics. JS owns stock and is a member of the Scientific Advisory Board of Surface Oncology, and is a member of the Scientific Advisory Board of Domain Therapeutics. RT has research grants to his institution from: Varian Medical Systems, Elekta Oncology, Accuray, Inc; scientific advisory board member for: Reflexion Medical, ImmuneSensor Therapeutics. AW acknowledge funding from AstraZeneca and imCORE. RW has stock and other ownership interests with Boost Therapeutics, Immvira LLC, Reflexion Pharmaceuticals, Coordination Pharmaceuticals Inc., Magi Therapeutics, Oncosenescence, Aqualung Therapeutics Corporation, and Cyntegron; he has served in a consulting or advisory role for Aettis Inc., AstraZeneca, Coordination Pharmaceuticals, Genus, Merck Serono S.A., Nano Proteagen, NKGen Biotech, Shuttle Pharmaceuticals, Highlight Therapeutics, S.L., Aqualung Therapeutics Corporation; he has research grants with Varian and Regeneron. RZ is scientific advisory board member of iTeos Therapeutics, receives research grant support from Bristol Myers Squibb and AstraZeneca, and is inventor on patent applications related to work on GITR, CTLA-4, and PD-1 (patent numbers: US20180244793A1; US10323091B2; WO2018106864A1; WO2019094352A1). SD has received compensation for consultant/advisory services from Lytix Biopharma, Mersana Therapeutics, EMD Serono, Ono Pharmaceutical, and Genentech, and research support from Lytix Biopharma and Boehringer-Ingelheim for unrelated projects. LG is/has been holding research contracts with Lytix Biopharma, Promontory and Onxeo, has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Imvax, Sotio, Promontory, Noxopharm, EduCom, and the Luke Heller TECPR2 Foundation, and holds Promontory stock options. ED reports grants and personal fees from Roche Genentech; grants from Servier; grants from AstraZeneca; grants and personal fees from Merck-Serono; grants from BMS; and grants from MSD outside the submitted work. SCF has Consultant: Bayer, Bristol Myers Squibb, Varian, ViewRay, Accuray, Elekta, Janssen, Regeneron, GlaxoSmithKline, Eisai, Astra Zeneca, MedImmune, Merck US, EMD Serono/Merck, Genentech/ROCHE, Boehringer Ingelheim, Nanobiotix and Grant/Research: support from: Bristol Myers Squibb, Varian, Regeneron, Merck, Celldex. All other authors have no conflict of interest to declare.

Figures

**Figure 1.**
Persisting challenges for radiotherapy and immunotherapy combinations. We surmise that the successful implementation of radiotherapy (RT) and immunotherapy (IT) combinations to a wide spectrum of oncological indications will require an improved understanding of the impact of dose and fractionation on the immunogenicity or RT, the design of treatment fields that spare circulating lymphocytes and tumor-draining lymph nodes (TDLNs), at least initially, the identification of optimal treatment schedules to maximize the interaction between RT and IT (which may depend on tumor type and specific immunotherapeutic agent) and an advanced characterization of the immunobiological effects of charged particles.

See this image and copyright information in PMC

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Updates on radiotherapy-immunotherapy combinations: Proceedings of 6^th annual ImmunoRad conference

Affiliations

Updates on radiotherapy-immunotherapy combinations: Proceedings of 6^th annual ImmunoRad conference

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical