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:Innovative immunotherapeutic strategies for thyroid cancer: challenges and opportunities.
甲状腺癌是全球第七大常见癌症,发病率和死亡率不断上升。
甲状腺癌是全球第七大常见癌症,发病率和死亡率不断上升。这种恶性肿瘤包含具有不同生物学行为、临床结局和治疗脆弱性的不同亚型。虽然大多数甲状腺癌病例预后良好,对手术和放射性碘治疗等常规疗法反应良好,但晚期、复发或去分化亚型预后差且治疗选择有限,因此需要开发更有效的治疗策略。尽管免疫治疗策略在多种恶性肿瘤中取得了显著进展,但这些方法在甲状腺癌中的转化相对缓慢且不一致。除免疫检查点抑制剂(ICI)治疗外,其他类型的免疫治疗在甲状腺癌中尚未推进至早期临床试验之后。这归因于甲状腺肿瘤的内在特性,其被广泛认为是冷肿瘤,具有低突变负荷和高免疫抑制性肿瘤微环境(TME)。尽管如此,近期研究表明,通过了解不同甲状腺癌亚型的免疫生物学,可以使免疫治疗策略适应其独特的分子、细胞和微环境特征,从而提高治疗效果。本综述旨在讨论甲状腺癌各种免疫治疗方法的进展和缺陷,包括ICI治疗、过继细胞治疗(CAR-T细胞、TCR-T细胞和TIL治疗)、溶瘤病毒治疗以及巨噬细胞/髓系调节免疫治疗。对亚型特异性免疫生物学的更深入理解以及免疫治疗干预的精准定制,可能最终为晚期甲状腺癌患者带来更有效且持久的临床缓解。
Thyroid cancer is the seventh most prevalent cancer worldwide, with a growing incidence and mortality rate. This malignancy encompasses distinct subtypes with diverse biological behaviors, clinical outcomes, and therapeutic vulnerabilities. While most thyroid cancer cases are associated with a favorable prognosis and respond well to conventional therapies, such as surgery and radioactive iodine therapy, advanced, recurrent, or dedifferentiated subtypes have a bad prognosis and limited therapeutic options, necessitating the development of more efficacious therapeutic strategies. Despite the remarkable progress of immunotherapeutic strategies across multiple malignancies, the translation of these approaches into thyroid cancer has been comparatively slow and inconsistent. Except for immune checkpoint inhibitor (ICI) therapy, other types of immunotherapy in thyroid cancer have not yet been advanced beyond early-stage clinical trials. This is attributed to the intrinsic nature of thyroid tumors, which are widely considered cold tumors with low mutational burden and a high immunosuppressive tumor microenvironment (TME). Nonetheless, recent studies indicate that by understanding the immunobiology of different subtypes of thyroid cancers, immunotherapeutic strategies can be adapted to their unique molecular, cellular, and microenvironmental characteristics, thereby improving therapeutic efficacy. This review aims to discuss the progress and pitfalls of various immunotherapy approaches for thyroid cancer, including ICI therapies, adoptive cell therapies (CAR-T cell, TCR-T cell, and TIL therapy), oncolytic virotherapy, and macrophage/myeloid-modulating immunotherapies. A deeper understanding of subtype-specific immunobiology and precise tailoring of immunotherapeutic interventions may ultimately enable more effective and durable clinical responses for patients with advanced thyroid cancer.
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