Search

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.

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: 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., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

The last several years have revealed increasing evidence of the immunomodulatory role of radiation therapy. Radiotherapy reshapes the tumoral microenvironment can shift the balance toward a more immunostimulatory or immunosuppressive microenvironment. The immune response to radiation therapy appears to depend on the irradiation configuration (dose, particle, fractionation) and delivery modes (dose rate, spatial distributions). Although an optimal irradiation configuration (dose, temporal fractionation, spatial dose distribution, etc.) has not yet been determined, temporal schemes employing high doses per fraction appear to favor radiation-induced immune response through immunogenic cell death. Through the release of damage-associated molecular patterns and the sensing of double-stranded DNA and RNA breaks, immunogenic cell death activates the innate and adaptive immune response, leading to tumor infiltration by effector T cells and the abscopal effect. Novel radiotherapy approaches such as FLASH and spatially fractionated radiotherapies (SFRT) strongly modulate the dose delivery method. FLASH-RT and SFRT have the potential to trigger the immune system effectively while preserving healthy surrounding tissues. This manuscript reviews the current state of knowledge on the immunomodulation effects of these two new radiotherapy techniques in the tumor, healthy immune cells and non-targeted regions, as well as their therapeutic potential in combination with immunotherapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The extra-embryonic yolk sac contains the first definitive multipotent hematopoietic cells, denominated erythromyeloid progenitors. They originate in situ prior to the emergence of hematopoietic stem cells and give rise to erythroid, monocytes, granulocytes, mast cells and macrophages, the latter in a Myb transcription factor-independent manner. We uncovered here the heterogeneity of yolk sac erythromyeloid progenitors, at the single cell level, and discriminated multipotent from committed progenitors, prior to fetal liver colonization. We identified two temporally distinct megakaryocyte differentiation pathways. The first occurs in the yolk sac, bypasses intermediate bipotent megakaryocyte-erythroid progenitors and, similar to the differentiation of macrophages, is Myb-independent. By contrast, the second originates later, from Myb-dependent bipotent progenitors expressing Csf2rb and colonize the fetal liver, where they give rise to megakaryocytes and to large numbers of erythrocytes. Understanding megakaryocyte development is crucial as they play key functions during vascular development, in particular in separating blood and lymphatic networks., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the embryo, the first hematopoietic cells derive from the yolk sac and are thought to be rapidly replaced by the progeny of hematopoietic stem cells. We used three lineage-tracing mouse models to show that, contrary to what was previously assumed, hematopoietic stem cells do not contribute significantly to erythrocyte production up until birth. Lineage tracing of yolk sac erythromyeloid progenitors, which generate tissue resident macrophages, identified highly proliferative erythroid progenitors that rapidly differentiate after intra-embryonic injection, persisting as the major contributors to the embryonic erythroid compartment. We show that erythrocyte progenitors of yolk sac origin require 10-fold lower concentrations of erythropoietin than their hematopoietic stem cell-derived counterparts for efficient erythrocyte production. We propose that, in a low erythropoietin environment in the fetal liver, yolk sac-derived erythrocyte progenitors efficiently outcompete hematopoietic stem cell progeny, which fails to generate megakaryocyte and erythrocyte progenitors., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2021 Soares-da-Silva et al.)