Ablative radiation alone in stage i lung cancer produces an adaptive systemic immune response: Insights from a prospective stud

Khinh Ranh Voong, Peter B. Illei, Bradley Presson, Dipika Singh, Zhen Zeng, Mara Lanis, Russell K. Hales, Chen Hu, Phuoc T. Tran, Christos Georgiades, Cheng Ting Lin, Jeffrey Thiboutout, Julie R. Brahmer, Patrick M. Forde, Jarushka Naidoo, Valsamo Anagnostou, Kellie N. Smith

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere007188
JournalJournal for immunotherapy of cancer
Volume11
Issue number10
DOIs
StatePublished - Oct 4 2023

Keywords

  • CD8-positive T-lymphocytes
  • adaptive immunity
  • non-small cell lung cancer
  • radiotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Immunology and Allergy
  • Pharmacology
  • Immunology

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