γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Gamma delta (γδ) T cells in cancer immunotherapy; where it comes from, where it will go?
Gamma delta (γδ) T cells in cancer immunotherapy; where it comes from, where it will go?
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癌症免疫治疗是近期针对癌细胞的治疗方法中备受关注的领域,因为它可以利用宿主免疫系统的资源来对抗入侵的肿瘤细胞。在癌症免疫治疗中,αβT 细胞在一段时间内发挥着基础性作用;然而,它们对主要组织相容性复合体(MHC)的依赖性、仅能识别突变肽的能力,以及对肿瘤部位尤其是实体瘤的低趋向性,为其进入临床设置带来了障碍。目前,γδT 细胞——作为免疫系统固有免疫和适应性免疫之间桥梁的细胞——在癌症免疫治疗中重新引起了关注。γδT 细胞已被证明可诱导对癌细胞的抗肿瘤效应,但对正常细胞无此作用。其遗传结构也使其易于进行治疗干预的操作。γδT 细胞能够以 MHC 依赖性和非依赖性方式识别广泛的抗原,如脂质、磷酸抗原和肽;这表明这些细胞也可能对突变负荷低和 MHC 下调的肿瘤发挥抗肿瘤效应。尽管看似有前景,但不应忘记,γδT 细胞在癌症研究中的应用仍相对处于起步阶段,许多挑战和障碍尚待识别。在本综述中,我们讨论了基于 γδT 细胞的免疫治疗在人类癌症中的优势及挑战,并提出新技术如何能够解决这些局限性。
Cancer immunotherapy is a field of interest in the recent treatment approaches against cancer cells, as it could use the assets of the host's immune system against the invading tumor cells. In cancer immunotherapy, for a while, αβT cells play fundamental roles; however, their dependence on major histocompatibility complex (MHC), their ability to only recognize mutated peptides, as well as their low tropism to the tumor sites, especially in solid tumors, have put an obstacle on their way into the clinical settings. Currently, a renewed interest has focused on γδT cells -cells that act as a bridge between the innate and adaptive arm of the immune system- in cancer immunotherapy. γδT cells have been shown to induce anti-tumor effects in cancer cells, but not in normal cells.
Their genetic structure also allows easy manipulation for therapeutic interventions. γδT cells could recognize a wide range of antigens, such as lipids, phospho-antigens, and peptides, in MHC-dependent and -independent manner; suggesting that these cells could also exert anti-tumor effects against tumors with low mutational burdens and downregulated MHC.
Although seems promising, it should not be forgotten that the application of γδT cells in cancer research is relatively at its infancy and many challenges and hurdles are yet to be identified. In the present review, we discuss the advantages as well as the challenges of γδT cells-based immunotherapies in human cancer and propose how new technologies could solve these limitations.
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