Abstract B035: Lymphocyte Subpopulation Balances as a Blood Biomarker for Immune-Related Adverse Events in Patients Receiving Immune Checkpoint Inhibitors

Abstract Background Immune-related adverse events (irAEs) are a major concern for cancer patients treated with immune checkpoint inhibitors (ICIs) and difficult to predict due to the current lack of reliable clinical biomarkers. While irAEs can usually be resolved with immunosuppressive drugs, this comes at the expense of decreasing ICI-induced anti-tumor immunity. Tertiary lymphoid structures (TLS) and T follicular helper cells (Tfh) have been shown to play an important role in tumor control and are linked with B cells and ICI responsiveness. Tfh cells play key roles in autoimmunity, B cell activation, immunoglobulin production, Th1-skewed CD4+ and cytotoxic CD8+ T cell effector activities, suggesting they could be associated with irAE pathogenesis. Methods Blood samples from ICI-treated patients with solid tumors (n=35) enrolled in our ongoing prospective trial (NCT05429866) were analyzed. Blood was collected at baseline (pre-ICI), periodically on treatment and at any irAE onset (grades 1-4) before intervention for immunophenotyping by flow cytometry. Results The patient group included the following solid tumors: melanoma (n=14), non-small cell lung cancer (n=10), endometrial cancer (n=4), breast cancer (n=3), gastrointestinal cancer (n= 1), head and neck cancer (n=1), renal cell carcinoma (n=1) and urothelial cancer (n=1), treated with ICI alone (n=21) or ICI plus chemotherapy (n=14). At 12 months of follow-up, 47.1% experienced an irAE with 80.8% grade 1-2 and 19.2% grade 3-4. Neutrophil counts (P=0.02), the neutrophil/lymphocyte ratio (P=0.05) and the systemic immune-inflammation index were low at baseline in patients experiencing an irAE. Blood immune cell monitoring indicated that increases in the percentage of total CD4+ cells (P=0.03), specifically in Th1 (P=0.04) and Tfh1 (P=0.01) cells, along with decreases in Th17 (P=0.003) and Tfh17 (P=0.03) cells, were significantly associated with irAEs both at baseline and after 8-11 weeks of treatment. In patients experiencing toxicities, there was an increase in eosinophil counts (P=0.001) and Tfh1 cells (P=0.01) and a corresponding decrease in Tfh17 cells compared to baseline levels at the time of toxicity. Conclusions Changes in the relative balance of neutrophils, eosinophils and specific CD4+ T cell subpopulations were linked with irAEs. Our ongoing studies shall include analysis of cytokine and gene expression changes in relation to these subpopulation alterations. This study is a first step toward identifying biomarkers that anticipate irAE onset and consequently may have the potential to reduce the need for immediate immunosuppressive treatments that compromise ICI efficacy. Citation Format: Mireille Diane LANGOUO FONTSA, Mario STABILE, Andrea Garavello, Pauline Delvaux, Anouk Goudsmit, Thierry Berghmans, Mariana Brandão, Jeremy Blanc, Maxime lzkovitz, Anne-Pascale Meert, Anaïs Boisson, Doïna Sofronii, Thila Vanhulst, Soizic Garaud, Françine Padonou Abogunde, Ahmad Awada, Karen Willard-Gallo. Lymphocyte Subpopulation Balances as a Blood Biomarker for Immune-Related Adverse Events in Patients Receiving Immune Checkpoint Inhibitors [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B035.