Emerging roles for tumor stroma in antigen presentation and anti-cancer immunity.
Emerging roles for tumor stroma in antigen presentation and anti-cancer immunity.
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DOI：
10.1042/bst20221083
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发表时间：
2023-12-20
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
过去十年免疫疗法的进步彻底改变了多种癌症诊断的治疗模式。然而，只有少数患者获得持久的益处，并且癌症疫苗等传统方法的进展仍然不令人满意。克服这些障碍的关键在于更深入地了解肿瘤抗原呈递以及肿瘤浸润抗原呈递细胞（APC）复杂且动态的异质性。让人想起 Klaus Ley 提出的 CD4+ T 细胞分化的“第二次接触”假说，淋巴结引发的 CD8+ T 细胞要获得全部效应潜力，需要在抗原起源的部位（即肿瘤床）进行第二轮共刺激。肿瘤基质在此过程中发挥着重要作用，它拥有专门的 APC 微环境，明显不同于三级淋巴结构，支持第二次抗原接触和 CD8+ T 细胞效应器增殖和分化。我们建议，二次接触生态位内的 APC 可以通过基质衍生的指导信号模拟胚胎或伤口愈合临时基质重塑来进行共刺激。基质的这些免疫刺激作用与其作为物理和功能性“免疫屏障”的广泛接受的观点形成鲜明对比。基质对抗原呈递的控制具有进化意义，因为宿主基质-肿瘤界面构成了针对新兴肿瘤的稳态“防御”的首要防线。在这篇综述中，我们概述了基质衍生的信号和细胞如何调节肿瘤床中的肿瘤抗原呈递和 T 细胞效应分化。将肿瘤基质重新定义为免疫变阻器而不是僵化的免疫屏障，这蕴藏着重要的未开发的治疗机会。
Advances in immunotherapy in the last decade have revolutionized treatment paradigms across multiple cancer diagnoses. However, only a minority of patients derive durable benefit and progress with traditional approaches, such as cancer vaccines, remains unsatisfactory. A key to overcoming these barriers resides with a deeper understanding of tumor antigen presentation and the complex and dynamic heterogeneity of tumor-infiltrating antigen-presenting cells (APCs). Reminiscent of the ‘second touch' hypothesis proposed by Klaus Ley for CD4+ T cell differentiation, the acquisition of full effector potential by lymph node- primed CD8+ T cells requires a second round of co-stimulation at the site where the antigen originated, i.e. the tumor bed. The tumor stroma holds a prime role in this process by hosting specialized APC niches, apparently distinct from tertiary lymphoid structures, that support second antigenic touch encounters and CD8+ T cell effector proliferation and differentiation. We propose that APC within second-touch niches become licensed for co-stimulation through stromal-derived instructive signals emulating embryonic or wound-healing provisional matrix remodeling. These immunostimulatory roles of stroma contrast with its widely accepted view as a physical and functional ‘immune barrier'. Stromal control of antigen presentation makes evolutionary sense as the host stroma-tumor interface constitutes the prime line of homeostatic ‘defense' against the emerging tumor. In this review, we outline how stroma-derived signals and cells regulate tumor antigen presentation and T-cell effector differentiation in the tumor bed. The re-definition of tumor stroma as immune rheostat rather than as inflexible immune barrier harbors significant untapped therapeutic opportunity.
影响因子：
15.3
作者：
LEE, G;ELLINGSWORTH, LR;GILLIS, S;WALL, R;KINCADE, PW
通讯作者：
KINCADE, PW
影响因子：
--
作者：
Nandadasa S;Burin des Roziers C;Koch C;Tran-Lundmark K;Dours-Zimmermann MT;Zimmermann DR;Valleix S;Apte SS
通讯作者：
Apte SS
影响因子：
5.2
作者：
Kim S;Karin M
通讯作者：
Karin M