Abstract Therapeutic strategies for chronic hepatitis B (CHB) aim to achieve functional cure, specifically defined by sustained off-treatment elimination of hepatitis B virus (HBV) surface antigen. New treatment approaches are being developed to enhance HBV-specific immune responses to reach this goal. To better understand how checkpoint blockade works in CHB, we conducted single-cell sequencing analysis of blood samples from four patients who either responded or did not respond to a single dose of nivolumab (an anti-PD-1 therapy). We examined cells at baseline and at two subsequent timepoints during treatment. Our findings revealed that a patient who achieved functional cure displayed higher baseline levels of stem cell-like memory CD8+ T cells, along with increases in CD8+ T effector cells, CD8+ T effector memory cells, and CD4+ T cells that reexpress CD45RA at 24 weeks after nivolumab administration. Additionally, we observed the emergence of specific T and B cell clones during treatment that correlated with positive response. These clones were identified within CD8 T effector, CD8 T effector memory, CD4 T memory cells re-expressing CD45RA, and memory B cell populations. Notably, some prominent memory B cell clones had not undergone isotype switching, indicating the development of new B cell responses rather than modification of existing immune responses. These results suggest that certain T cell phenotypes in peripheral blood, together with specific clonal expansions of T and B cells, may indicate successful clinical response to checkpoint blockade therapy in CHB. Developing treatments that specifically enhance these immune mechanisms may lead to more effective therapeutic strategies.
Kim et al. (Wed,) studied this question.