FOXP3⁺ 细胞富集微环境与复发/难治性 B 细胞淋巴瘤 CAR-T 细胞治疗后更优的总生存期相关

CAR-T cell therapy has revolutionized the treatment of non-Hodgkin B-lymphomas, but relapse rates remain unacceptably high, and resistance mechanisms are still unclear. A key challenge of T-cell-based therapy is the immune-suppressive tumor microenvironment, which is rich in immune-suppressive cells, including regulatory T cells (Tregs). Tregs express FOXP3, CD3 and CD25, and their role in B-cell lymphomas treated with CAR-T cells remains uncertain.

Using immunohistochemistry, we analyzed 31 pre-infusion and seven post-infusion paired biopsies from patients with relapsed/refractory B-cell lymphoma who received CAR-T cell therapy. Pre- infusion FOXP3+ cell percentages were assessed and correlated with response rate, progression-free survival (PFS), and overall survival (OS). Post-infusion biopsies were examined for FOXP3 changes.

We identified 3% as the optimal FOXP3+ cut-off, defining low ( 3%) and high (>3%) FOXP3 groups. Patients with high FOXP3 had a better OS (1-year OS 94% versus 61%, P = 0. 006). PFS also favored high FOXP3 patients but lacked statistical significance (1-year PFS 65% versus 54%, P = 0. 41).

Notably, relapsed patients with high FOXP3 maintained high expression and responded better to subsequent treatments (P = 0. 03).

Our findings highlight the impact of tumor-infiltrating Tregs on CAR-T cell efficacy in lymphomas.