# The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment

## TL;DR

This study explores immune cell changes in blood of Hodgkin lymphoma patients undergoing anti-PD1 treatment to understand why some respond well and others do not.

## Contribution

The study identifies a specific CD8+ T cell subset linked to successful anti-PD1 treatment responses in Hodgkin lymphoma patients.

## Key findings

- A stable KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell phenotype is associated with complete remission in cHL patients.
- Responder patients show clonal expansion of TCR clonotypes in the identified CD8+ T cell subset.
- Longitudinal analysis reveals evolving immune responses during anti-PD1 therapy in R/R cHL patients.

## Abstract

Checkpoint blockade therapy (CBT) involving anti-PD1 antibodies represents the standard approach for cHL patients who do not respond to second-line therapy. Nonetheless, only 20% of relapsed/refractory (R/R) cHL patients treated with CBT achieve complete remission. In this study, we extensively examined the immune dynamics in eight R/R cHL patients treated with CBT, consisting of four complete responders (CR) and four experiencing disease progression (PD), by single cell analysis of peripheral blood mononuclear cells (PBMCs). Our unique approach encompassed longitudinal analysis with three time points, providing a comprehensive understanding of the evolving immune responses during anti-PD1 therapy. Through gene expression profiling, we identified a stable and distinctive KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell phenotype in patients achieving complete responses. This specific CD8+ T cell subset exhibited sustained activation, underscoring its potential pivotal role in mounting an effective immune response against cHL. Furthermore, T cell receptor (TCR) analysis revealed that in responder patients there is clonal expansion between TCR clonotypes specifically in the KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell subset. Our longitudinal study offers unique insights into the complex immune dynamics of multiply relapsed/highly pre-treated cHL patients undergoing anti-PD1 therapy.