Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model

Nakamura, 1990, Radiosensitivity of CD4 or CD8 positive human T-lymphocytes by an in vitro colony formation assay, Radiat Res, 123, 224, 10.2307/3577549 Ellsworth, 2018, Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors, Adv Radiat Oncol, 3, 512, 10.1016/j.adro.2018.08.014 Dai, 2022, The impact of radiation induced lymphopenia in the prognosis of head and neck cancer: A systematic review and meta-analysis, Radiother Oncol Damen, 2021, The influence of severe radiation-induced lymphopenia on overall survival in solid tumors: a systematic review and meta-analysis, Int J Radiat Oncol Biol Phys, 111, 936, 10.1016/j.ijrobp.2021.07.1695 Upadhyay, 2021, Risk and impact of radiation related lymphopenia in lung cancer: A systematic review and meta-analysis, Radiother Oncol, 157, 225, 10.1016/j.radonc.2021.01.034 Shiraishi, 2018, Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy, Radiother Oncol, 128, 154, 10.1016/j.radonc.2017.11.028 Routman, 2019, A comparison of grade 4 lymphopenia with proton versus photon radiation therapy for esophageal cancer, Adv Radiat Oncol, 4, 63, 10.1016/j.adro.2018.09.004 Alexandru, 2021, Assessing the spleen as an organ at risk in radiation therapy and its relationship with radiation-induced lymphopenia: A retrospective study and literature review, Adv Radiat Oncol, 6 Jin, 2020, Ultra-high dose rate effect on circulating immune cells: A potential mechanism for FLASH effect?, Radiother Oncol, 149, 55, 10.1016/j.radonc.2020.04.054 Biau, 2019, Selection of lymph node target volumes for definitive head and neck radiation therapy: a 2019 update, Radiother Oncol, 134, 1, 10.1016/j.radonc.2019.01.018 Loganadane, 2020, Comparison of nodal target volume definition in breast cancer radiation therapy according to RTOG versus ESTRO atlases: a practical review from the TransAtlantic Radiation Oncology Network (TRONE), Int J Radiat Oncol Biol Phys, 107, 437, 10.1016/j.ijrobp.2020.04.012 Hall, 2021, NRG oncology updated international consensus atlas on pelvic lymph node volumes for intact and postoperative prostate cancer, Int J Radiat Oncol Biol Phys, 109, 174, 10.1016/j.ijrobp.2020.08.034 Dodwell, 2019, GS4 Koontz, 2020, Shifting the curtain—can we make sense of the whole pelvis controversy?, Int J Radiat Oncol Biol Phys, 106, 534, 10.1016/j.ijrobp.2019.11.012 Ladbury, 2019, Anal cancer in the era of dose painted intensity modulated radiation therapy: Implications for regional nodal therapy Poortmans, 2020, Internal mammary and medial supraclavicular lymph node chain irradiation in stage I–III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial, Lancet Oncol, 21, 1602, 10.1016/S1470-2045(20)30472-1 Senkus, 2021, De-escalation of axillary irradiation for early breast cancer–Has the time come?, Cancer Treat Rev, 101, 10.1016/j.ctrv.2021.102297 Weiner, 2019, National practice patterns for lymph node irradiation in 197,000 men receiving external beam radiotherapy for localized prostate cancer Ossetrova, 2014, Early-response biomarkers for assessment of radiation exposure in a mouse total-body irradiation model, Health Phys, 106, 772, 10.1097/HP.0000000000000094 Blakely, 2014, Further biodosimetry investigations using murine partial-body irradiation model, Radiat Prot Dosim, 159, 46, 10.1093/rpd/ncu127 Qu, 2010, 2-Gy whole-body irradiation significantly alters the balance of CD4+ CD25− T effector cells and CD4+ CD25+ Foxp3+ T regulatory cells in mice, Cellular Molecular Immunol, 7, 419, 10.1038/cmi.2010.45 Kroemer, 2013, Immunogenic cell death in cancer therapy, Annu Rev Immunol, 31, 51, 10.1146/annurev-immunol-032712-100008 Wennerberg, 2017, Barriers to radiation-induced in situ tumor vaccination, Front Immunol, 8, 229, 10.3389/fimmu.2017.00229 Mondini, 2020, Radiotherapy–immunotherapy combinations–perspectives and challenges, Molecular Oncology, 14, 1529, 10.1002/1878-0261.12658 Verhaegen, 2018, ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges, Radiother Oncol, 126, 471, 10.1016/j.radonc.2017.11.016 Telarovic, 2020, Probing spatiotemporal fractionation on the preclinical level, Phys Med Biol, 65, 22NT02, 10.1088/1361-6560/abbb75 Butterworth, 2017, Modelling responses to spatially fractionated radiation fields using preclinical image-guided radiotherapy, Br J Radiol, 90, 10.1259/bjr.20160485 Sievert, 2018, Improved overall survival of mice by reducing lung side effects after high-precision heart irradiation using a small animal radiation research platform, Int J Radiat Oncol Biol Phys, 101, 671, 10.1016/j.ijrobp.2018.02.017 Ghita, 2019, Preclinical evaluation of dose-volume effects and lung toxicity occurring in and out-of-field, Int J Radiat Oncol Biol Phys, 103, 1231, 10.1016/j.ijrobp.2018.12.010 van Hoof, 2013, Development and validation of a treatment planning system for small animal radiotherapy: SmART-Plan, Radiother Oncol, 109, 361, 10.1016/j.radonc.2013.10.003 Gao, 2015, High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response, Nat Med, 21, 1318, 10.1038/nm.3954 Ivashkevich, 2012, Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research, Cancer Lett, 327, 123, 10.1016/j.canlet.2011.12.025 Dewan, 2009, Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti–CTLA-4 antibody, Clin Cancer Res, 15, 5379, 10.1158/1078-0432.CCR-09-0265 Chen, 2020, Absolute lymphocyte count predicts abscopal responses and outcomes in patients receiving combined immunotherapy and radiation therapy: analysis of 3 phase 1/2 trials, Int J Radiat Oncol Biol Phys, 108, 196, 10.1016/j.ijrobp.2020.01.032 Lambin, 2020, Lymphocyte-sparing radiotherapy: the rationale for protecting lymphocyte-rich organs when combining radiotherapy with immunotherapy, Semin Radiat Oncol, 10.1016/j.semradonc.2019.12.003 Ganusov, 2021, Experimental and mathematical approaches to quantify recirculation kinetics of lymphocytes. Mathematical, 151 Ellsworth, 2014, Sustained CD4+ T cell-driven lymphopenia without a compensatory IL-7/IL-15 response among high-grade glioma patients treated with radiation and temozolomide, Oncoimmunology, 3, e27357, 10.4161/onci.27357 Cao, 2011, Different radiosensitivity of CD4+ CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro, Int J Radiat Biol, 87, 71, 10.3109/09553002.2010.518208 Beauford, 2020, Ionizing radiation modulates the phenotype and function of human CD4+ induced regulatory T cells, BMC immunology, 21, 1 Heylmann, 2021, Comparison of DNA repair and radiosensitivity of different blood cell populations, Sci Rep, 11, 2478, 10.1038/s41598-021-81058-1 Heylmann, 2014, Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells, Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1846, 121, 10.1016/j.bbcan.2014.04.009 Cheng, 2021, Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy, Sci Adv, 7, eabc7609, 10.1126/sciadv.abc7609 Buchwald, 2020, Tumor-draining lymph node is important for a robust abscopal effect stimulated by radiotherapy, J Immunother Cancer, 8, 10.1136/jitc-2020-000867 Marciscano, 2018, Elective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapy, Clin Cancer Res, 24, 5058, 10.1158/1078-0432.CCR-17-3427 O'Melia, 2021, Tumor-draining lymph nodes are survival niches that support T cell priming against lymphatic transported tumor antigen and effects of immune checkpoint blockade in TNBC, Cancer Immunol, Immunotherapy, 1 Byun, 2021, Effect of interleukin-7 on radiation-induced lymphopenia and its antitumor effects in a mouse model, Int J Radiat Oncol* Biol* Phys, 109, 1559, 10.1016/j.ijrobp.2020.12.004 Du, 2018, A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy, Cell Res, 28, 416, 10.1038/s41422-018-0011-0 Sharma, 2019, Anti-CTLA-4 immunotherapy does not deplete FOXP3+ regulatory T cells (Tregs) in human cancers, Clin Cancer Res, 25, 1233, 10.1158/1078-0432.CCR-18-0762 Quezada, 2019, Lost in translation: deciphering the mechanism of action of anti-human CTLA-4, Clin Cancer Res, 25, 1130, 10.1158/1078-0432.CCR-18-2509