CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:NGAL as a Potential Target in Tumor Microenvironment.
NGAL as a Potential Target in Tumor Microenvironment.
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癌细胞与间质细胞之间的信号网络在肿瘤微环境中发挥关键作用。肿瘤进展的命运很大程度取决于自肿瘤转化之初,这些细胞群之间交换的大量信息。干预这类信号已为癌症治疗带来令人振奋的结果,例如免疫检查点抑制剂抗PD-1、抗PD-L1和抗CTLA-4抗体可阻断癌细胞对免疫细胞施加的抑制信号,CAR-T 技术则可促进部分白血病和淋巴瘤患者抗肿瘤免疫重新激活。然而,许多癌症,尤其是实体瘤,仍对这些疗法耐药。因此,在肿瘤分泌组中识别新的分子靶点,有助于进一步完善当前抗癌治疗策略。中性粒细胞明胶酶相关脂质运载蛋白(NGAL)是一种分泌蛋白,在多种人类肿瘤分泌组中大量表达。NGAL在癌细胞和间质细胞内部以及二者相互作用中发挥多种作用,因此是一个有前景的靶点。本综述聚焦NGAL在肿瘤微环境及癌症衰老相关分泌表型(SASP)中的不同作用,强调可能用于癌症治疗的关键功能。
The signaling network between cancer and stromal cells plays a crucial role in tumor microenvironment. The fate of tumor progression mainly depends on the huge amount of information that these cell populations exchange from the onset of neoplastic transformation. Interfering with such signaling has been producing exciting results in cancer therapy: just think of anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies that, acting as immune checkpoint inhibitors, interrupt the inhibitory signaling exerted by cancer cells on immune cells or the CAR-T technology that fosters the reactivation of anti-tumoral immunity in a restricted group of leukemias and lymphomas.
Nevertheless, many types of cancers, in particular solid tumors, are still refractory to these treatments, so the identification of novel molecular targets in tumor secretome would benefit from implementation of current anti-cancer therapeutical strategies. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a secreted protein abundantly expressed in the secretome of various human tumors.
It represents a promising target for the multiple roles that are played inside cancer and stromal cells, and also overall in their cross-talk. The review focuses on the different roles of NGAL in tumor microenvironment and in cancer senescence-associated secretory phenotype (SASP), highlighting the most crucial functions that could be eventually targetable in cancer therapy.
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