小柯机器人

美国芝加哥大学Justin Kline研究小组近期取得重要工作进展，他们研究发现树突状细胞可通过主要组织相容性复合物“变装”引发抗肿瘤CD8⁺ T细胞应答。该项研究成果2022年5月25日在线出版于《免疫》杂志上。

在这里，研究人员证明MHC-I“变装”，是一种抗原呈递途径，DC在其中获得并展示完整的肿瘤来源的肽：MHC-I分子，在协调抗肿瘤免疫方面也很重要。在两种皮下肿瘤模型中，最佳CD8⁺ T细胞活化需要肿瘤细胞MHC-I表达。DCs在体内获得肿瘤来源的肽：MHC-I分子足以诱导抗原特异性CD8⁺ T细胞启动。在体外和人类肿瘤异种移植物中检测到肿瘤衍生的人类白细胞抗原（HLA）分子向骨髓细胞的转移。总之，MHC-I“变装”对于DC引发的抗肿瘤CD8⁺ T细胞至关重要。除了定量增强肿瘤抗原呈递外，MHC“变装”还可能使DC更忠实和有效地反映癌细胞多肽组。

据介绍，抗原交叉呈递，其中树突状细胞 (DC) 在主要组织相容性 I 类 (MHC-I) 分子上呈递外源性抗原，被认为是DC启动肿瘤特异性CD8⁺ T细胞应答的主要机制。

附：英文原文

Title: Dendritic cells can prime anti-tumor CD8+ T cell responses through major histocompatibility complex cross-dressing

Author: Brendan W. MacNabb, Sravya Tumuluru, Xiufen Chen, James Godfrey, Darshan N. Kasal, Jovian Yu, Marlieke L.M. Jongsma, Robbert M. Spaapen, Douglas E. Kline, Justin Kline

Issue&Volume: 2022-05-25

Abstract: Antigen cross-presentation, wherein dendritic cells (DCs) present exogenous antigenon major histocompatibility class I (MHC-I) molecules, is considered the primary mechanismby which DCs initiate tumor-specific CD8+ T cell responses. Here, we demonstrate that MHC-I cross-dressing, an antigen presentationpathway in which DCs acquire and display intact tumor-derived peptide:MHC-I molecules,is also important in orchestrating anti-tumor immunity. Cancer cell MHC-I expressionwas required for optimal CD8+ T cell activation in two subcutaneous tumor models. In vivo acquisition of tumor-derived peptide:MHC-I molecules by DCs was sufficient to induceantigen-specific CD8+ T cell priming. Transfer of tumor-derived human leukocyte antigen (HLA) moleculesto myeloid cells was detected in vitro and in human tumor xenografts. In conclusion, MHC-I cross-dressing is crucial foranti-tumor CD8+ T cell priming by DCs. In addition to quantitatively enhancing tumor antigen presentation,MHC cross-dressing might also enable DCs to more faithfully and efficiently mirrorthe cancer cell peptidome.

DOI: 10.1016/j.immuni.2022.04.016

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00187-X

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