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:Looking ahead to targeting macrophages by CAR T- or NK-cells in blood cancers.
针对血液系统恶性肿瘤肿瘤微环境免疫抑制状态的新型策略具有重要的临床意义,可能带来生存期延长、生活质量改善以及癌症治疗毒性降低。
引言:骨髓微环境(BME)对正常造血至关重要,但常在血液系统恶性肿瘤中受到破坏。肿瘤相关巨噬细胞(TAM)是肿瘤微环境(TME)的主要细胞类型,在肿瘤生长和进展中发挥重要作用。靶向TAM并调节其极化是有希望的癌症治疗策略。综述范围:本文讨论TME的重要性,以及多种可能用于调节免疫抑制性TAM的靶点,包括CD123、鞘氨醇-1-磷酸受体、CD19/CD1d、CCR4/CCL22、CSF1R(CD115)、CD24、CD40、B7家族蛋白、MARCO、CD47、CD163、CD204、CD206及叶酸受体。专家观点:采用创新方法对抗血液系统恶性肿瘤TME中的免疫抑制状态具有重要临床意义,可能延长生存、改善生活质量并降低癌症治疗毒性。标准治疗流程可能会将CAR-T/NK细胞疗法与其他治疗联合,从而实现更全面的癌症治疗。
INTRODUCTION: The bone marrow microenvironment (BME) is critical for healthy hematopoiesis and is often disrupted in hematologic malignancies. Tumor-associated macrophages (TAMs) are a major cell type in the tumor microenvironment (TME) and play a significant role in tumor growth and progression. Targeting TAMs and modulating their polarization is a promising strategy for cancer therapy. AREAS COVERED: In this review, we discuss the importance of TME and different multiple possible targets to modulate immunosuppressive TAMs such as: CD123, Sphingosine 1-Phosphate Receptors, CD19/CD1d, CCR4/CCL22, CSF1R (CD115), CD24, CD40, B7 family proteins, MARCO, CD47, CD163, CD204, CD206 and folate receptors. EXPERT OPINION: Innovative approaches to combat the immunosuppressive milieu of the tumor microenvironment in hematologic malignancies are of high clinical significance and may lead to increased survival, improved quality of life, and decreased toxicity of cancer therapies. Standard procedures will likely involve a combination of CAR T/NK-cell therapies with other treatments, leading to more comprehensive cancer care.
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