Host immune biomarkers associated with infection risk after CAR T-cell therapy

Reynolds, GK; Williams, L; Giner, G; Garnham, A; Jansen, T; Dowling, MR; Minson, A; Chee, L; Dickinson, M; Anderson, MA; Thursky, K; Oliaro, J; Harrison, SJ; Slavin, MA; Doerflinger, M; Teh, BW

Author(s): Reynolds, GK; Williams, L; Giner, G; Garnham, A; Jansen, T; Dowling, MR; Minson, A; Chee, L; Dickinson, M; Anderson, MA; Thursky, K; Oliaro, J; Harrison, SJ; Slavin, MA; Doerflinger, M; Teh, BW;
Details: Publication Year 2026-09-23,Volume 93,Issue #4,Page 106863
Journal Title: Journal of Infection
Abstract: BACKGROUND: Infection is the leading cause of non-relapse mortality after CAR-T therapy, yet individual risk prediction remains challenging. This exploratory study evaluated immune correlates of infection and other treatment-emergent adverse events in patients with diffuse large B-cell lymphoma (DLBCL) receiving CAR-T. METHODS: Twenty patients with relapsed or refractory DLBCL received axicabtagene ciloleucel (n = 7) or tisagenlecleucel (n = 13), with prospective blood collection at apheresis, (baseline), post-lymphodepletion, and day 30 (D30). Cytokine responses were assessed in stimulated peripheral blood mononuclear cells; transcriptomic profiling was performed using bulk RNA-seq. Infections were classified as early (apheresis-D30) or late (D30-D90). Associations between immune features and infection were explored using multivariable regression. RESULTS: Eighteen infections (13 early, 5 late) occurred in 11 patients (55%). Early infections were associated with higher baseline neutrophil activation cytokines (OR=4.35, p=0.047), lower TREM-1 levels following stimulation (OR=1.37 per 500 pg/mL decrease, p=0.004), and upregulation of heme metabolism genes. Late infections correlated with increased MCP-1 secretion (OR=1.82 per 500 pg/mL, p=0.013) and suppression of TNF-α-related pathways at D30. By D30, cytokine responses associated with Th1 (295 vs. 9365 pg/mL, p < 0.001), T-cell (263 vs. 531 pg/mL) and B-cell pathways (220 vs. 584 pg/mL) were significantly suppressed compared to baseline (p < 0.001) accompanied by transcriptomic downregulation of immune activation signatures. Distinct immune patterns were also observed in toxicity. CRS (grade ≥ 2) was linked to suppressed Th1 cytokines at D30 (IL-12: 3 vs. 403 pg/mL, p < 0.001) and RNASE1 overexpression, while ICANS (grade ≥ 1) was associated with increased Th1 cytokines (2368 vs. 1361 pg/mL, p=0.007), independent of corticosteroid use. CONCLUSIONS: Longitudinal immune profiling identified distinct immunological signatures linked to infection risk and CAR-T-related toxicities. These findings suggest a role for immune monitoring in improving risk stratification and guiding supportive care after CAR-T therapy.
Publisher: Elsevier
Keywords: Biomarkers; Car-t; Infection; Personalised medicine
Research Division(s): Infection and Global Health; Bioinformatics and Computational Biology; Blood Cells and Blood Cancer
PubMed ID: 42777835
Publisher's Version: https://doi.org/10.1016/j.jinf.2026.106863
Open Access at Publisher's Site: https://doi.org/ 10.1016/j.jinf.2026.106863
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-10-02 08:19:00

Last Modified: 2026-10-02 08:19:08