Ablative radiation alone in stage I lung cancer produces an adaptive systemic immune response: insights from a prospective stud
Stereotactic ablative body radiation (SABR) delivers high rates of local control in early-stage non-small cell lung cancer (NSCLC); however, systemic immune effects are poorly understood. 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 5-7 days after SABR (48 Gy/4 or 50 Gy/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 week and 3-6 months after SABR. SABR alone could induce a delayed, transient neoantigen-specific T-cell immunologic response in patients with stage I NSCLC.
Lung Cancer Research Foundation - 2017 LCRF Scientific Grant Program Award
The Mark Foundation for Cancer Research
Bloomberg-Kimmel Institute for Cancer Immunotherapy
The Mark Foundation Center for Advanced Genomics and Imaging
Lung Cancer Foundation of America
Swim Across America
National Institutes of Health R37CA251447, CA121113, U01CA212007, U01CA231776, R01CA271540, U54CA273956.
American Lung Association
CommentsThe original article is available at https://jitc.bmj.com/
Published CitationVoong KR. et al. Ablative radiation alone in stage I lung cancer produces an adaptive systemic immune response: insights from a prospective stud. J Immunother Cancer. 2023;11(10):e007188.
Publication Date4 October 2023
- Beaumont Hospital
PublisherBMJ Publishing Group Ltd.
- Published Version (Version of Record)