决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Unveiling the Role of Tumor-Infiltrating T Cells and Immunotherapy in Hepatocellular Carcinoma: A Comprehensive Review.
尽管医学不断进步,5 年生存率仍仅为惨淡的 18%,且 5 年内复发率高达令人却步的 70%。
肝细胞癌(HCC)是迅速加剧的全球健康问题,位列癌症相关死亡原因第三位。尽管医疗有所进步,HCC患者5年生存率仍仅为18%,且5年内复发率高达70%。包括一线药物索拉非尼在内的现行系统治疗,总客观缓解率(ORR)低于10%。相比之下,免疫疗法已显示出潜力,可将ORR提高至约30%。IMbrave150临床试验证明,阿替利珠单抗联合贝伐珠单抗在中位无进展生存期(PFS)和总生存期(OS)方面优于索拉非尼。然而,HCC患者的治疗效果仍不理想,亟需全面了解其抗肿瘤反应及免疫逃逸机制。因此,阐明HCC的免疫图景至关重要。肿瘤浸润T细胞,包括细胞毒性T细胞、调节性T细胞和自然杀伤T细胞,是抗肿瘤免疫反应的关键组成部分。本综述旨在阐明这些细胞在免疫抑制性肿瘤微环境中的复杂相互作用,并探讨恢复功能失调T细胞活性的潜在策略。此外,本文还总结了HCC当前基于免疫检查点抑制剂(ICI)的临床试验、ICI联合治疗以及CAR-T或TCR-T细胞疗法,这些策略未来有望进一步改善OS并改变HCC的治疗格局。
Hepatocellular carcinoma (HCC) is a rapidly rising global health concern, ranking as the third-leading cause of cancer-related mortality. Despite medical advancements, the five-year survival rate remains a dismal 18%, with a daunting 70% recurrence rate within a five-year period. Current systematic treatments, including first-line sorafenib, yield an overall response rate (ORR) below 10%. In contrast, immunotherapies have shown promise by improving ORR to approximately 30%. The IMbravel150 clinical trial demonstrates that combining atezolizumab and bevacizumab surpasses sorafenib in terms of median progression-free survival (PFS) and overall survival (OS). However, the therapeutic efficacy for HCC patients remains unsatisfactory, highlighting the urgent need for a comprehensive understanding of antitumor responses and immune evasion mechanisms in HCC. In this context, understanding the immune landscape of HCC is of paramount importance. Tumor-infiltrating T cells, including cytotoxic T cells, regulatory T cells, and natural killer T cells, are key components in the antitumor immune response. This review aims to shed light on their intricate interactions within the immunosuppressive tumor microenvironment and explores potential strategies for revitalizing dysfunctional T cells. Additionally, current immune checkpoint inhibitor (ICI)-based trials, ICI-based combination therapies, and CAR-T- or TCR-T-cell therapies for HCC are summarized, which might further improve OS and transform the management of HCC in the future.
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