P0133Distinct CD8+ T-cell immune signatures in UC patients under different biologic therapies: evidence of selective modulation by IL-12/23 inhibition

Background Biotechnological therapies have reshaped the management of Ulcerative Colitis by targeting distinct immune pathways; however, their differential effects on peripheral immune homeostasis remain poorly characterized. CD8+ T cells, key players in cytotoxic and regulatory responses, undergo dynamic changes in differentiation and activation during inflammation and treatment. To characterize the peripheral CD8+ T-cell subsets in UC patients receiving different biologic agents and to identify treatment-specific immune signatures and potential biomarkers of therapeutic response. Methods Peripheral blood samples from UC patients (n = 13) patients treated with anti-TNF (n = 4), Vedolizumab (n = 5), or Ustekinumab (n = 4), and from biologic-naïve controls (n = 5), were analyzed by flow cytometry using panels for T-memory and T-regulatory subsets. CD8+ T-cell populations were defined as naïve (CD8+CD45RA+CD95-CD197+), effector (Teff)(CD8+CD45RA+CD95+CD197-), effector memory (Tem)(CD8+CD45RA-CD95lowCD27-), and central memory (Tcm)(CD8+CD45RA-CD95lowCD27+). Data were normalized and compared using unpaired t-tests to assess differences between treatment groups and controls. Results Compared with controls, Ustekinumab induced a selective modulation characterized by a reduction in naïve (CD45RA+CD62L+CD197+) cells, indicative of a lower proportion of undifferentiated lymphocytes and a shift toward more advanced maturation, and an expansion of effector memory (CD45RA-CD62L-CD27+) and terminal effector (CD45RA-CD62L-CD197-) subsets (p-value < 0.05). This pattern reflects an increase in differentiated, functionally active CD8+ T cells potentially involved in inflammation control and mucosal repair. Such modulation was not observed in patients treated with anti-TNF or Vedolizumab, in whom these subsets remained overall stable. Conclusion These findings indicate IL-12/23 inhibition drives a distinct CD8+ T-cell remodeling, reflecting immune adaptation relevant for rapid mucosal healing and long-term therapeutic efficacy. This biologic-specific CD8+ T-cell signature may serve as a potential biomarker to predict therapeutic response and guide personalized treatment strategies in IBD. Conflict of interest: Mrs. Migliore, Greta: No conflict of interest Rumi, Gabriele: No conflict of interest Petito, Valentina: No conflict of interest Masi, Letizia: No conflict of interest Troisi, Sara: No conflict of interest Profeta, Francesca: No conflict of interest Pane, Cesare: No conflict of interest Lopetuso, Loris Riccardo: No conflict of interest gasbarrini, antonio: No conflict of interest Scaldaferri, Franco: No conflict of interest