Kikete Siambi, Luo Li, Jia Beitian, Wang Li, Ondieki Gregory, Bian Yuhong
Tianjin University of Traditional Chinese Medicine, No. 88, Yuquan Road, Nan Kai District, Tianjin, 300193, People's Republic of China.
Department of Rheumatology and Immunology, First Affiliated Hospital of Xinjiang Medical University, Ürümqi, 830000, People's Republic of China.
Cytotechnology. 2018 Aug;70(4):1097-1110. doi: 10.1007/s10616-018-0202-z. Epub 2018 Mar 19.
Today, cancers pose a major public health burden. Although a myriad of cancer treatments are available, only a few have achieved clinical efficacy. This is partly attributed to cancers capability to evade host immunity by converting dendritic cells (DCs) from potent stimulators to negative modulators of immunity. Dendritic cell-based immunotherapy attempts to resolve this problem by manipulating the functional characteristics of DCs. Plant-derived polysaccharides (PDPs) can stimulate the maturation of DCs conferring on them the capacity to present internalised tumorigenic antigens to naïve T cells and subsequently priming T cells to eliminate tumours. PDPs have been used as immune modulators and later as anti-cancer agents by Traditional Chinese Medicine practitioners for centuries. They are abundant in nature and form a large group of heterogeneous though structurally related macromolecules that exhibit diverse immunological properties. They can induce antigen pulsed DCs to acquire functional characteristics in vitro which can subsequently be re-introduced into cancer patients. They can also be used as adjuvants in DC-based vaccines or independently for their intrinsic anti-tumour activities. Clinically, some in vitro generated DCs have been shown to be both safe and immunogenic although their clinical application is limited in part by unsatisfactory functional maturation as well as impaired migration to draining lymph nodes where T cells reside. We review the relative potencies of individual PDPs to induce both phenotypic and functional maturation in DCs, their relative abilities to activate anti-cancer immunity, the possible mechanisms by which they act and also the challenges surrounding their clinical application.
如今,癌症构成了重大的公共卫生负担。尽管有无数种癌症治疗方法可供选择,但只有少数几种取得了临床疗效。这部分归因于癌症能够通过将树突状细胞(DCs)从强大的免疫刺激剂转变为免疫负调节剂来逃避宿主免疫。基于树突状细胞的免疫疗法试图通过操纵DCs的功能特性来解决这个问题。植物源多糖(PDPs)可以刺激DCs成熟,使其能够将内化的致瘤抗原呈递给幼稚T细胞,随后启动T细胞以消除肿瘤。几个世纪以来,PDPs一直被传统中医从业者用作免疫调节剂,后来又用作抗癌剂。它们在自然界中含量丰富,形成了一大类结构相关但性质各异的大分子,具有多种免疫特性。它们可以诱导抗原脉冲DCs在体外获得功能特性,随后可将其重新引入癌症患者体内。它们还可以用作基于DC的疫苗的佐剂,或因其固有的抗肿瘤活性而单独使用。临床上,一些体外生成的DCs已被证明既安全又具有免疫原性,尽管它们的临床应用部分受到功能成熟不理想以及向T细胞所在的引流淋巴结迁移受损的限制。我们综述了单个PDPs诱导DCs表型和功能成熟的相对效力、它们激活抗癌免疫的相对能力、它们发挥作用的可能机制以及围绕其临床应用的挑战。