2021年 · 第101卷第28期

follicular lymphoma (FL) is a class of indolent lymphoma, but its heterogeneity is strong. Numerous studies have shown that the prognosis of FL is closely related to its tumor microenvironment, with T cell infiltration positively correlated with good prognosis, and the heterogeneity of T cell composition and localization in tumors (including CD8⁺PD-1⁺or FoxP3⁺etc.) are related to efficacy. Therefore, it is particularly important to better understand the specific effects of each treatment on FL T cells to reach their full antitumor potential. Lenalidomide has been reported to activate CD8⁺T cells, inhibiting regulatory T cells (Treg), restoring the formation of T cell immune synapses, and downregulating T cell PD-1 expression. However, how effective these properties are in FL patients remains unclear, especially in the context of binding to anti-CD20 antibodies. To investigate the efficacy of otuzumab in combination with lenalidomide in patients with FL, the GALEN trial (otuzumab in combination with lenalidomide in relapsed/refractory FL) was conducted. The study included 71 patients with FL (44 first-line treatment and 27 relapsed/refractory), and their cellular phenotype, transcriptome and function were analyzed before and after treatment, respectively. The results showed that lenalidomide upregulated PD-1 and increased HLA-DR expression in both cases. highlighted the role of lenalidomide in PD-1⁺Peculiar patterns of transcriptomic modifications induced in vivo by FL T cells. This functional assessment suggests that lenalidomide triggers T cell proliferation without eliminating Treg activity. Lenalidomide triggers transient transformation of T cells into proliferative effector memory T cells. Lenalidomide repairs T-cell immune synapses in FL patients, while octuzumab does not antagonize or even prolong this effect.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovium of the joint. Compared with traditional drugs to improve rheumatism, glucocorticoids have the advantage of fast onset of action. Previous ACR and EULAR guidelines have recommended that low-dose glucocorticoids can be used as "bridge therapy" in the initiation treatment of RA. However, the use of glucocorticoids may bring side effects such as osteoporosis, inhibition of adrenal axis function and steroid diabetes to RA patients. Previous studies have shown that RA patients who continue to use low-dose prednisone can achieve better clinical efficacy, but there are currently no double-blind, randomized, placebo-controlled trials for specific low-dose prednisone reduction treatment regimens and continuous low-dose prednisone treatment regimens. The study used a multicenter randomized, double-blind trial to explore the clinical efficacy and safety of low-dose prednisone reduction versus continuous low-dose prednisone treatment in RA patients treated with tocilizumab. A total of 259 RA patients (including 200 women and 59 men) were enrolled in the study and randomized 1:1 to a continuous low-dose prednisone treatment group (oral prednisone 5 mg/d) and a reduced dose of prednisone treatment group (starting with prednisone 5 mg/d and reducing dose by 1 mg every 4 weeks). The mean change from baseline to week 24 in the DAS28 disease activity score in the prednisone taper group was 0.54 (95%CI: 0.35 to 0.73), whereas the mean change in DAS28 was-0.08 (95%CI: -0.27 to-0.12) [the difference between the two groups was 0.61 (95%CI：0.35~0.88），P<0.000 1］。 In addition, the incidence of RA disease activity (26% vs. 11%) and the probability of adverse events (5% vs. 3%) were lower in the sustained low-dose prednisone treatment group compared with the prednisone reduction group.