{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:58:25Z","timestamp":1793534305841,"version":"4.5.0"},"reference-count":52,"publisher":"Radiation Research Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2024,10,30]]},"abstract":"<jats:p>Radiation-induced lymphopenia (RIL) is associated with worse outcomes in patients with multiple solid tumors. Hypofractionated radiation therapy (HFRT) reduces RIL compared with conventionally fractionated radiation therapy (CFRT). However, fractionation effects on immune repertoire (IR) diversity are unknown. RNA-based T- and B-cell receptor sequencing was performed on peripheral lymphocytes collected prospectively before radiation therapy and &lt;4 weeks after the final radiation fraction. Patients received CFRT (\u22643 Gy\/day \u00d7 \u226510 days 6 chemotherapy, n = 13) or HFRT (\u22655 Gy\/day \u00d7 \u22645 days, n = 10), per institutional standards of care. Immune repertoire diversity parameters analyzed were number of unique CDR3 receptors (uCDR3), Shannon entropy, and sample clonality (percentage of all receptors represented by the top 10 clones). RIL was severe with concurrent chemotherapy (median %D ALC -58.8%, \u201312.5%, and \u201328.6% in patients treated with CFRT and chemo, CFRT alone, and HFRT, respectively). CFRT and concurrent chemotherapy was associated with more severe diversity restriction in all examined parameters than either HFRT or CFRT alone. Increased immune repertoire diversity despite decreased ALC was more common in patients treated with HFRT than CFRT and significantly less common in patients treated with concurrent chemotherapy (P &lt; 0.001). Radiation-induced changes in immune repertoire diversity are variably reflected in the peripheral ALC. Both HFRT and CFRT caused RIL, but HFRT was associated with improved immune repertoire diversity despite RIL. The addition of chemotherapy may potentiate radiation-induced restriction in immune repertoire diversity. As immune repertoire diversity is associated with response to immunotherapy, these findings may have implications for radiation therapy\/chemotherapy\/immunotherapy combinations. Further studies are required to understand the relationship between radiation, circulating lymphocyte populations, immune repertoire diversity and response to treatment.<\/jats:p>","DOI":"10.1667\/rade-24-00010.1","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:49:09Z","timestamp":1730249349000},"page":"837-846","source":"Crossref","is-referenced-by-count":6,"title":["Survey of Changes in Absolute Lymphocyte Counts and Peripheral Immune Repertoire Diversity after External Beam Radiotherapy"],"prefix":"10.1667","volume":"202","author":[{"given":"Susannah G.","family":"Ellsworth","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R. Y.","family":"Shiue","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Murthy","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda L.","family":"Byrne-Steel","sequence":"additional","affiliation":[{"name":"iRepertoire, Inc., Huntsville, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Zellars","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Ming (Spring)","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Hong Kong University School of Clinical Medicine, Pokfulam Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A.","family":"Russ","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Lotze","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"29","doi-asserted-by":"crossref","unstructured":"SC Formenti, NP Rudqvist, E Golden, et al.  \"Nat Med.\"  24, \"Radiotherapy induces responses of lung cancer to CTLA-4 blockade.\" 1845 (2018)","DOI":"10.1038\/s41591-018-0232-2"},{"key":"13","doi-asserted-by":"crossref","unstructured":"S Yovino, L Kleinberg, SA Grossman, et al.  \"Cancer Invest.\"  31, \"The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells.\" 140 (2013)","DOI":"10.3109\/07357907.2012.762780"},{"key":"11","doi-asserted-by":"crossref","unstructured":"MA Postow, MK Callahan, CA Barker, et al.  \"N Engl J Med.\"  366, \"Immunologic correlates of the abscopal effect in a patient with melanoma.\" 925 (2012)","DOI":"10.1056\/NEJMoa1112824"},{"key":"12","doi-asserted-by":"crossref","unstructured":"SG. 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