IL-6 receptor inhibition promotes expansion of cytolytic CD4+ T cells after cellular immunotherapy.

IL-6 receptor inhibition during cellular immunotherapy enhances cytolytic CD4+ T-cell differentiation, including Eomes+ subsets linked to improved antitumor effects.

• Why it matters: Understanding how IL-6 signaling influences immune responses during HSCT is crucial because its dysregulation promotes GVHD, a major complication, yet its effects in patients remain unclear.
• What they did: Single-cell RNA sequencing was performed on circulating CD14+ monocytes and CD4+ T cells from patients in a clinical trial of IL-6R inhibition (tocilizumab or placebo), analyzing immune programs and T-cell differentiation.
• The result: IL-6R inhibition promoted type I interferon-associated transcriptional programs and profoundly increased cytolytic CD4+ T-cell differentiation, including Eomes+ subsets, which may improve immunotherapy outcomes and antitumor responses.