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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms.
LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms.
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白细胞相关免疫球蛋白样受体1(LAIR1,也称CD305)属于免疫抑制性受体家族,广泛表达于成熟造血细胞,尤其是免疫细胞。已发现LAIR1有四类配体,其中包括胶原蛋白,提示其可能通过细胞外基质发挥免疫调节作用。LAIR1可调控细胞因子分泌和细胞功能,在NK细胞以及T、B淋巴细胞的不同亚群中,随分化和活化呈现不同表达模式,并发挥重要的负向免疫调节作用。除参与正常生理过程外,LAIR1功能异常还与多种自身免疫性或炎症性疾病有关,并参与癌症(包括血液系统恶性肿瘤)的病理生理过程。作为抑制性受体,LAIR1可导致免疫细胞应答失调,并促进肿瘤微环境中的免疫逃逸。若由肿瘤细胞表达,LAIR1还可调节肿瘤细胞增殖或侵袭能力;其促肿瘤或抑肿瘤作用因肿瘤类型而异。本文综述LAIR1在正常生理状态及包括血液系统恶性肿瘤在内的病理状态中的作用,并讨论靶向LAIR1治疗自身免疫性疾病和癌症的潜在策略。
Leukocyte-associated immunoglobulin (Ig)-like receptor 1 (LAIR1, CD305) belongs to the family of immune-inhibitory receptors and is widely expressed on hematopoietic mature cells, particularly on immune cells. Four different types of ligands of LAIR1 have been described, including collagens, suggesting a potential immune-regulatory function on the extracellular matrix. By modulating cytokine secretion and cellular functions, LAIR1 displays distinct patterns of expression among NK cell and T/B lymphocyte subsets during their differentiation and cellular activation and plays a major negative immunoregulatory role.
Beyond its implications in physiology, the activity of LAIR1 can be inappropriately involved in various autoimmune or inflammatory disorders and has been implicated in cancer physiopathology, including hematological neoplasms. Its action as an inhibitory receptor can result in the dysregulation of immune cellular responses and in immune escape within the tumor microenvironment.
Furthermore, when expressed by tumor cells, LAIR1 can modulate their proliferation or invasion properties, with contradictory pro- or anti-tumoral effects depending on tumor type. In this review, we will focus on its role in normal physiological conditions, as well as during pathological situations, including hematological malignancies.
We will also discuss potential therapeutic strategies targeting LAIR1 for the treatment of various autoimmune diseases and cancer settings.
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