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:Adenosine-A2A Receptor Pathway in Cancer Immunotherapy.
Adenosine-A2A Receptor Pathway in Cancer Immunotherapy.
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A2A受体(A2AR)是一种对腺苷具有高亲和力的典型G蛋白偶联受体(GPCR),在多种免疫细胞中表达,如调节性T细胞、细胞毒性T细胞和巨噬细胞等。腺苷与A2AR结合后会激活典型G蛋白并触发cAMP/PKA/CREB通路。腺苷-A2AR通路可保护正常器官和组织免受免疫细胞自身免疫反应损伤。然而,许多实体瘤通过促进腺苷蓄积劫持腺苷-A2AR通路。A2AR通路激活会抑制免疫细胞的免疫应答,进而促进肿瘤细胞在肿瘤微环境中免疫逃逸。近期动物实验和临床试验均提示,阻断腺苷通路可抑制多种实体瘤进展。此外,A2AR阻断联合CAR-T 细胞疗法显示出更好的抗肿瘤疗效,令人鼓舞。因此,本文将讨论腺苷-A2AR通路在肿瘤微环境中的作用,并总结近期A2AR与癌症相关研究进展。
A2A receptors (A2AR), a typical GPCR with a high affinity for adenosine, was expressed in many immune cells, such as regulatory T cells, cytotoxic T cells, macrophages, etc. Adenosine binding to the A2AR receptor activates the typical G protein and triggers the cAMP/PKA/CREB pathway. The adenosine-A2AR pathway plays an important role in protecting normal organs and tissues from the autoimmune response of immune cells.
However, many solid tumors hijack the adenosine-A2AR pathway by promoting adenosine accumulation. The activation of the A2AR pathway inhibited the immune response of immune cells and then promotes the immune escape of tumor cells in the tumor microenvironment. Recently, both animal experiments and clinical trials indicated that blocking the adenosine pathway can inhibit the progression of a variety of solid tumors.
In addition, it is encouraging that A2AR blockade combined with CAR T cells therapy showed better anti-tumor efficacy.
Therefore, this review will discuss the role of the adenosine-A2AR pathway in the tumor microenvironment and summarize recent advances of A2AR-cancer related studies.
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