Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy.
Br J Haematol. 2023 Nov;203(4):564-570. doi: 10.1111/bjh.19117. Epub 2023 Oct 3.
CD4 and CD8 chimeric antigen receptor T cells (CAR-T) play different roles in the in vivo anti-tumour response, but the role of the CD4 /CD8 ratio among infused CAR-T has not been clearly defined yet. We analysed leftovers from infused anti-CD19 CAR-T bags of 31 patients with aggressive B-cell lymphomas. The median ratio was 1.44, lower for brexu-cel compared to tisa-cel and axi-cel. The CAR+CD4 /CD8 ratio was influenced by lactate dehydrogenase levels at apheresis, not by age, previous treatments or the CD4 /CD8 ratio in peripheral blood. Patients with a response at 3 months after CAR-T (M3) had a lower CAR+CD4 /CD8 ratio in the infused products compared to non-responders (ratio 0.74 vs. 2.47, p = 0.011). A CAR+CD4 /CD8 ratio higher than the cut point of 1.12 was associated with an increased risk of treatment failure at M3 (OR 23.3, p = 0.012) and M6 (OR 10, p = 0.028). The median 6-month PFS was 76% for patients with a ratio lower than 1.12% vs. 31% for the others. The prognostic role of the CAR+CD4 /CD8 ratio was independent of the costimulatory domain (CD28 vs. 4-1BB) of the product (OR 16.41, p = 0.041). Our data indicate a crucial role for CD8 CAR-T and the CAR+CD4 /CD8 ratio in predicting CAR-T efficacy.
CD4 和 CD8 嵌合抗原受体 T 细胞 (CAR-T) 在体内抗肿瘤反应中发挥不同作用，但输注的 CAR-T 中的 CD4/CD8 比值的作用尚未明确。我们分析了 31 例侵袭性 B 细胞淋巴瘤患者输注的抗 CD19 CAR-T 袋中的剩余物。中位比值为 1.44，brexu-cel 低于 tisa-cel 和 axi-cel。CAR+CD4/CD8 比值受采集时乳酸脱氢酶水平的影响，而不受年龄、既往治疗或外周血 CD4/CD8 比值的影响。CAR-T 后 3 个月（M3）有反应的患者与无反应的患者相比，输注产品中的 CAR+CD4/CD8 比值较低（比值 0.74 对 2.47，p=0.011）。CAR+CD4/CD8 比值高于 1.12 的截点与 M3（OR 23.3，p=0.012）和 M6（OR 10，p=0.028）治疗失败的风险增加相关。CAR+CD4/CD8 比值低于 1.12%的患者中位 6 个月 PFS 为 76%，而其他患者为 31%。CAR+CD4/CD8 比值的预后作用独立于产品的共刺激结构域（CD28 与 4-1BB）（OR 16.41，p=0.041）。我们的数据表明 CD8 CAR-T 和 CAR+CD4/CD8 比值在预测 CAR-T 疗效方面起着关键作用。
