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Here, we evaluate the early pathologic and immunologic effects of SABR. Blood\/core-needle tumor biopsies were collected from six patients with stage I NSCLC before and 5\u20137\u2009days after SABR (48\u2009Gy\/4 or 50\u2009Gy\/5 fractions). Serial blood was collected up to 1-year post-SABR. We used immunohistochemistry to evaluate pathological changes, immune-cell populations (CD8, FoxP3), and PD-L1\/PD-1 expression within the tumor. We evaluated T-cell receptor (TCR) profile changes in the tumor using TCR sequencing. We used the MANAFEST (Mutation-Associated Neoantigen Functional Expansion of Specific T-cells) assay to detect peripheral neoantigen-specific T-cell responses and dynamics. At a median follow-up of 40 months, 83% of patients (n=5) were alive without tumor progression. Early post-SABR biopsies showed viable tumor and similar distribution of immune-cell populations as compared with baseline samples. Core-needle samples proved insufficient to detect population-level TCR-repertoire changes. Functionally, neoantigen-specific T-cells were detected in the blood prior to SABR. A subset of these patients had a transient increase in the frequency of neoantigen-specific T-cells between 1\u2009week and 3\u20136 months after SABR. SABR alone could induce a delayed, transient neoantigen-specific T-cell immunologic response in patients with stage I NSCLC.<\/jats:p>","DOI":"10.1136\/jitc-2023-007188","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T14:30:56Z","timestamp":1696429856000},"page":"e007188","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Ablative radiation alone in stage I lung cancer produces an adaptive systemic immune response: insights from a prospective study"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7753-1211","authenticated-orcid":false,"given":"Khinh Ranh","family":"Voong","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B","family":"Illei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Presson","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipika","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"The Mark Foundation Center for Advanced Genomics and Imaging, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"The Mark Foundation Center for Advanced Genomics and Imaging, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Lanis","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell K","family":"Hales","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Quantitative Sciences, Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuoc T","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Georgiades","sequence":"additional","affiliation":[{"name":"Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-8037","authenticated-orcid":false,"given":"Cheng Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Thiboutout","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R","family":"Brahmer","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M","family":"Forde","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins 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