Background: Immune checkpoint blockade can provide clinical benefit for patients with advanced cancer. Here, we report durable disease control over many years following PD-L1 blockade through induction of a viral antigen-specific T cell response in an adult patient with recurrent respiratory papillomatosis.
Methods: Antigen-specific T cell response assays, single cell RNA-sequencing, and RNA-scope was used to study clinical tissues.
Results: An HPV6 E2-specific T cell clone restricted to HLA-B*55, present at low frequency in the pre-treatment papilloma, significantly expanded after six doses of PD-L1 blockade and remained present and functional at the site of initial response in the larynx as a tissue resident memory T cell for 4 years. An associated reduction in E2 target gene was observed following treatment.
Conclusions: Although demonstrated in a single exceptional responder, these results highlight that immune checkpoint blockade may induce durable, viral antigen-specific immunity of sufficient magnitude to control disease in patients with nonmalignant disorders.
Keywords: PD-L1; human papillomavirus type 6; immune checkpoint blockade; recurrent respiratory papillomatosis; resident memory T cell.
© 2022 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.