小柯机器人

美国哈佛大学Vijay K. Kuchroo等研究人员合作发现调节抗肿瘤免疫力的B细胞特异性检查点分子。相关论文于2023年6月21日在线发表于国际学术期刊《自然》。

研究人员利用高通量流式细胞仪以及大量和单细胞RNA测序和B细胞受体测序分析B16F10黑色素瘤生长过程中的B细胞时间，并确定了一个B细胞亚群，该亚群在肿瘤小鼠的引流淋巴结中随着时间的推移而扩张。不断扩张的B细胞亚群表达细胞表面分子T细胞免疫球蛋白和粘液结构域1（TIM-1，由Havcr1编码）和一个独特的转录特征，包括多个共抑制分子，如PD-1、TIM-3、TIGIT和LAG-3。

尽管条件性删除B细胞上的这些共同抑制分子对肿瘤负担几乎没有影响，但选择性地删除B细胞中的Havcr1既能大幅抑制肿瘤生长，又能增强效应性T细胞反应。TIM-1的缺失增强了B细胞中的1型干扰素反应，这增强了B细胞的激活，增加了抗原呈递和共刺激，导致肿瘤特异性效应T细胞的扩张。这些结果表明，操纵表达TIM-1的B细胞能使适应性免疫的第二臂参与促进抗肿瘤免疫和抑制肿瘤生长。

据了解，B细胞在抗肿瘤免疫中的作用仍有争议，因此，免疫疗法主要是针对T细胞和自然杀伤细胞来抑制肿瘤生长。

附：英文原文

Title: B-cell-specific checkpoint molecules that regulate anti-tumour immunity

Author: Bod, Lloyd, Kye, Yoon-Chul, Shi, Jingwen, Torlai Triglia, Elena, Schnell, Alexandra, Fessler, Johannes, Ostrowski, Stephen M., Von-Franque, Max Y., Kuchroo, Juhi R., Barilla, Rocky M., Zaghouani, Sarah, Christian, Elena, Delorey, Toni Marie, Mohib, Kanishka, Xiao, Sheng, Slingerland, Nadine, Giuliano, Christopher J., Ashenberg, Orr, Li, Zhaorong, Rothstein, David M., Fisher, David E., Rozenblatt-Rosen, Orit, Sharpe, Arlene H., Quintana, Francisco J., Apetoh, Lionel, Regev, Aviv, Kuchroo, Vijay K.

Issue&Volume: 2023-06-21

Abstract: The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth, we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice. The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1, encoded by Havcr1) and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden, selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses. Loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumour-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth.

DOI: 10.1038/s41586-023-06231-0

Source: https://www.nature.com/articles/s41586-023-06231-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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