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However, recent studies have shown that RT can have potent immunomodulatory properties, which include both the ability to re\u2010program the tumour microenvironment (TME) and the activation of systemic anti\u2010tumour immune responses. It reviews the immune mechanisms involved in the killing of tumours after irradiation, such as immunogenic cell death (ICD), activation of the cGAS\u2013STING (cyclic GMP\u2013AMP synthase\u2013stimulator of interferon genes) pathway, dendritic cell (DC) maturation, priming of cytotoxic T lymphocytes (CTLs), and the abscopal effect, which refers to the regression of non\u2010irradiated tumours following local irradiation. We also discuss how RT induces immunosuppressive counterforces such as regulatory T cells (Tregs), myeloid\u2010derived suppressor cells (MDSCs), and programmed death\u2010ligand 1 (PD\u2010L1) upregulation. The synergy between RT and immune checkpoint inhibitors (ICIs) such as anti\u2010programmed cell death protein 1 (anti\u2010PD\u20101), anti\u2010programmed death\u2010ligand 1 (anti\u2010PD\u2010L1), and anti\u2010cytotoxic T\u2010lymphocyte\u2010associated protein 4 (anti\u2010CTLA\u20104) agents is critically assessed. We also discuss possible clinically relevant enhancement of side effects of immunotherapies by RT. The induction of neo\u2010antigens and immune activation by chemotherapy (ChX) versus RT is compared\/contrasted. Particular focus is paid to dose fractionation approaches, such as stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS), and their differential immunogenic effects. The different tumour types that are most susceptible to radiotherapy\u2010induced immunologic responses are covered in great detail, particularly malignant melanoma. The field is contextualised with relevant clinical trials, emerging patents, and translational case studies. In this review, we seek to give an integrative framework for how radiation\u2010induced immune reprogramming can be harnessed in the design of next\u2010generation precision oncology strategies.<\/jats:p>","DOI":"10.1111\/imm.70155","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:01:21Z","timestamp":1780416081000},"page":"37-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunological Reprogramming by Radiation Therapy: Implications for Precision Cancer Treatment"],"prefix":"10.1111","volume":"179","author":[{"given":"Arun Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"University School of Pharmaceutical Sciences, Rayat Bahra University  Mohali Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikash Chand","family":"Sharma","sequence":"additional","affiliation":[{"name":"Mody University of Science and Technology  Sikar Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"KIET School of Pharmacy, Krishna Institute of Engineering &amp; Technology  Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6579-2203","authenticated-orcid":false,"given":"Manoj Kumar","family":"Mishra","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy, Amity University Madhya Pradesh  Gwalior Madhya Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_13_4_1","volume-title":"Global Cancer Observatory: Cancer Today [Internet]","author":"World Health Organization","year":"2024"},{"issue":"6","key":"e_1_2_13_5_1","first-page":"797","article-title":"Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability\u2010Adjusted Life\u2010Years for 29 Cancer Groups, 1990 to 2021: A Systematic Analysis for the Global Burden of Disease Study 2021","volume":"9","author":"Fitzmaurice C.","year":"2023","journal-title":"JAMA Oncology"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MA00556B"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1296091"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S568254"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12030288"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2820"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4485"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.728.11.2"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2041"},{"key":"e_1_2_13_14_1","first-page":"87","article-title":"Deceleration of Carcinogenic Potential by Adaptation With Low Dose Gamma Irradiation","volume":"15","author":"Bhattacharjee D.","year":"2001","journal-title":"In Vivo"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1667\/RR2160.1"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2003.12.006"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90208-3"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2003.1.473"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2005.06.032"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/SMJ.0b013e3181ddd571"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/107327480401100307"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.8.2489"},{"key":"e_1_2_13_23_1","first-page":"119","article-title":"Immunological Aspects of Local Radiotherapy: Clinical Relevance","volume":"9","author":"Formenti S. 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