Hematopathology Division, Department of Pathology, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
Leuk Lymphoma. 2020 Dec;61(13):3038-3051. doi: 10.1080/10428194.2020.1805113. Epub 2020 Aug 25.
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell lymphoma and highly heterogeneous disease. With the standard immunochemotherapy, anti-CD20 antibody rituximab (R-) plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, 30-40% of DLBCLs are refractory to initial immunochemotherapy or experience relapse post-therapy with poor clinical outcomes despite salvage therapies. Mechanisms underlying chemoresistance and relapse are heterogeneous across DLBCL and within individual patients, representing hurdles for targeted therapies targeting a specific oncogenic signaling pathway. In recent years, paradigm-shifting immunotherapies have shown impressive efficacy in various cancer types regardless of underlying oncogenic mechanisms. Vaccines are being developed for DLBCL to build protective immunity against relapse after first complete remission and to promote antitumor immune responses synergizing with immune checkpoint inhibitors to treat refractory/relapsed patients. This article provides a brief review of current progress in vaccine development in DLBCL and discussion on immunologic mechanisms underlying the therapeutic effectiveness and resistance.
弥漫性大 B 细胞淋巴瘤(DLBCL)是最常见的侵袭性 B 细胞淋巴瘤,具有高度异质性。采用标准的免疫化学疗法,即抗 CD20 抗体利妥昔单抗(R)联合 CHOP(环磷酰胺、多柔比星、长春新碱和泼尼松)化疗,30-40%的 DLBCL 对初始免疫化学疗法具有耐药性,或在治疗后出现复发,尽管采用挽救疗法,但临床结局仍较差。导致化疗耐药和复发的机制在 DLBCL 之间以及在个体患者中具有异质性,这代表了针对特定致癌信号通路的靶向治疗的障碍。近年来,免疫疗法在各种癌症类型中显示出令人瞩目的疗效,无论潜在的致癌机制如何。目前正在开发针对 DLBCL 的疫苗,以在首次完全缓解后建立针对复发的保护性免疫,并促进与免疫检查点抑制剂协同的抗肿瘤免疫反应,以治疗耐药/复发患者。本文简要综述了 DLBCL 疫苗开发的最新进展,并讨论了治疗有效性和耐药性的免疫机制。