Pinco Paola, Facciotti Federica
Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
Cells. 2025 May 15;14(10):720. doi: 10.3390/cells14100720.
Unconventional T (UC T) cells, including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, γδ T cells, and double-negative (DN) T cells, are key players in immune surveillance and response due to their properties combining innate-like and adaptive-like features. These cells are widely present in mucosal tissues, where they can rapidly respond to infections and tumor-associated changes. In fact, UC T cells can have both pro- and anti-tumoral effects, with their activity influenced by factors such as microbial composition and the tumor microenvironment. In particular, intratumoral microbiota significantly impacts the development, function, and activation of UC T cells, influencing cytokine production and shaping the immune response in various cancers. The complex crosstalk between UC T cells and the surrounding factors is discussed in this review, with a focus on how these cells might be interesting candidates to explore and exploit as anticancer therapeutic agents. However, the great potential of UC T cells, not only demonstrated in the context of adoptive cell transfer, but also enhanced through techniques of engineering, is still flanked by different challenges, like the immunosuppressive tumor microenvironment and heterogeneity of target molecules associated with some specific categories of tumors, like gastrointestinal cancers.
非常规T（UCT）细胞，包括不变自然杀伤T（iNKT）细胞、黏膜相关不变T（MAIT）细胞、γδT细胞和双阴性（DN）T细胞，因其兼具固有样和适应性样特征，在免疫监视和应答中发挥着关键作用。这些细胞广泛存在于黏膜组织中，能够对感染和肿瘤相关变化迅速做出反应。事实上，UCT细胞可产生促肿瘤和抗肿瘤两种效应，其活性受微生物组成和肿瘤微环境等因素影响。特别是肿瘤内微生物群对UCT细胞的发育、功能和激活有显著影响，进而影响细胞因子的产生，并塑造各种癌症中的免疫应答。本综述讨论了UCT细胞与周围因素之间复杂的相互作用，重点关注这些细胞作为抗癌治疗药物进行探索和利用的潜在价值。然而，UCT细胞不仅在过继性细胞转移方面展现出巨大潜力，还可通过工程技术得到增强，但其仍面临不同挑战，如免疫抑制性肿瘤微环境以及与某些特定类型肿瘤（如胃肠道癌症）相关的靶分子异质性。
