Abstract C022: T-cell IL-6 expression defines a subset of memory T cells, and correlates with response to immune checkpoint inhibitors in patients with melanoma

Abstract While immune checkpoint inhibitors (ICIs) have revolutionized the treatment for various types of cancer, they benefit only a subset of patients, are costly, and may cause serious immune-related adverse events. Therefore, biomarkers that can predict their efficacy are urgently needed. Growing evidence has shown that an early on-treatment decrease of serum/plasma interleukin 6 (IL-6) level is associated with response to ICIs and improved survival in several types of cancer. However, the causes and mechanisms underlying changes in IL-6 during ICI therapy remain unclear. Here, using a modified method of intracellular staining for flow cytometry, we found a subset of peripheral blood (PB) CD3+ T cells that express IL-6 without ex vivo stimulation. This subset can be identified within CD45RA– CCR7+ central memory T cells (Tcm) and CD45RA– CCR7– effector memory T cells (Tem), but not in CD45RA+ CCR7+ naïve T cells (Tn) or CD45RA+ CCR7– terminally effector memory re-expressing antigenic cells (Temra). This subset is also found in melanoma-infiltrating T cells. IL-6 is expressed in proliferating T cells upon activation with anti-CD3/CD28 antibody or monocyte-derived dendritic cells in the presence of peptide pool of major histocompatibility complex class I- or II-restricted epitopes. Importantly, an early on-treatment decrease of PB IL-6+ T cells correlates with response and better progression-free and overall survival in patients with melanoma. Collectively, these results suggest that PB IL-6+ T cells may be a novel population that present transversally in memory T cells, and changes in their frequency may serve as an early predictor of treatment response in patients receiving ICIs. Citation Format: Hisashi Kanemaru, Ryutaro Kajihara, Paul K. Wallace, Brahm H. Segal, Gino K. In, Igor Puzanov, Mark S. Ernstoff, Fumito Ito. T-cell IL-6 expression defines a subset of memory T cells, and correlates with response to immune checkpoint inhibitors in patients with melanoma abstract. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C022.