Despite advancements in cancer immunotherapy, most lymphomas remain unresponsive to checkpoint inhibitors. P-selectin glycoprotein ligand-1 (PSGL-1), recently identified as a promoter of T-cell exhaustion in murine melanoma models, has emerged as a novel immune checkpoint protein and promising immunotherapeutic target. In this study, we investigated the potential of PSGL-1 antibody targeting in B-cell lymphoma. Using allogeneic co-culture systems, we demonstrated that targeted antibody interventions against human PSGL-1 enhanced T-cell activation and effector cytokine production in response to lymphoma cells. Moreover, in vitro treatment of primary lymphoma cell suspensions with PSGL-1 antibody resulted in increased activation of autologous lymphoma-infiltrating T cells. Using the A20 syngeneic B-cell lymphoma mouse model, we found that PSGL-1 antibody treatment significantly slowed tumor development and reduced the endpoint tumor burden. This antitumoral effect was accompanied by augmented tumor infiltration of CD4⁺ and CD8⁺ T cells and reduced infiltration of regulatory T cells. Finally, anti-PSGL-1 administration enhanced the expansion of CAR T cells previously transferred to mice bearing the aggressive Eμ-Myc lymphoma cells and improved disease control. These results demonstrate that PSGL-1 antibody blockade bolsters T-cell activity against B-cell lymphoma, suggesting a potential novel immunotherapeutic approach for treating these malignancies.

尽管癌症免疫疗法取得了进展，但大多数淋巴瘤仍然对检查点抑制剂无反应。P-选择素糖蛋白配体-1 （PSGL-1） 最近在小鼠黑色素瘤模型中被确定为 T 细胞耗竭的促进子，已成为一种新型免疫检查点蛋白和有前途的免疫治疗靶点。在这项研究中，我们研究了 PSGL-1 抗体靶向 B 细胞淋巴瘤的潜力。使用同种异体共培养系统，我们证明针对人 PSGL-1 的靶向抗体干预增强了响应淋巴瘤细胞的 T 细胞活化和效应细胞因子的产生。此外，用 PSGL-1 抗体对原发性淋巴瘤细胞悬液进行体外处理导致自体淋巴瘤浸润性 T 细胞的活化增加。使用 A20 同基因 B 细胞淋巴瘤小鼠模型，我们发现 PSGL-1 抗体治疗显着减缓了肿瘤发展并降低了终点肿瘤负荷。这种抗肿瘤作用伴随着 CD4 ⁺ 和 CD8 ⁺ T 细胞的肿瘤浸润增加，调节性 T 细胞浸润减少。最后，抗 PSGL-1 给药增强了先前转移到携带侵袭性 Eμ-Myc 淋巴瘤细胞的小鼠的 CAR T 细胞的扩增并改善了疾病控制。这些结果表明，PSGL-1 抗体阻断可增强 T 细胞对抗 B 细胞淋巴瘤的活性，这表明一种治疗这些恶性肿瘤的潜在新型免疫治疗方法。