AUTHOR=Coffey David G. , Xu Yuexin , Towlerton Andrea M. H. , Kowanetz Marcin , Hegde Priti , Darwish Martine , Yadav Mahesh , Blanchette Craig , Ruppert Shannon M. , Bertino Sarah , Xu Qikai , Ferretti Andrew , Weinheimer Adam , Hellmann Matthew , Qin Angel , Thomas Dafydd , Warren Edus H. , Ramnath Nithya TITLE=Case report: A persistently expanded T cell response in an exceptional responder to radiation and atezolizumab for metastatic non-small cell lung cancer JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.961105 DOI=10.3389/fimmu.2022.961105 ISSN=1664-3224 ABSTRACT=

Most patients with advanced non-small cell lung cancer (NSCLC) do not achieve a durable remission after treatment with immune checkpoint inhibitors. Here we report the clinical history of an exceptional responder to radiation and anti-program death-ligand 1 (PD-L1) monoclonal antibody, atezolizumab, for metastatic NSCLC who remains in a complete remission more than 8 years after treatment. Sequencing of the patient’s T cell repertoire from a metastatic lesion and the blood before and after anti-PD-L1 treatment revealed oligoclonal T cell expansion. Characterization of the dominant T cell clone, which comprised 10% of all clones and increased 10-fold in the blood post-treatment, revealed an activated CD8+ phenotype and reactivity against 4 HLA-A2 restricted neopeptides but not viral or wild-type human peptides, suggesting tumor reactivity. We hypothesize that the patient’s exceptional response to anti-PD-L1 therapy may have been achieved by increased tumor immunogenicity promoted by pre-treatment radiation therapy as well as long-term persistence of oligoclonal expanded circulating T cells.