CD155 mutation (Ala67Thr) increases the binding affinity for and the signaling via an inhibitory immunoreceptor TIGIT.
CD155 mutation (Ala67Thr) increases the binding affinity for and the signaling via an inhibitory immunoreceptor TIGIT.
复制标题
作者：
CD155是激活和抑制免疫受体DNAX辅助分子1(dNaM-1)(又称CD226)和T细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域(TIGIT)的共同配体，表达在自然杀伤细胞(NK细胞)和T细胞上，分别对肿瘤免疫反应起正向和负向调节作用。最近的一项研究表明，单核苷酸多态rs1058402G>；A导致CD155 67位ALA突变为Thr，与小细胞肺癌患者的总体生存率下降有关，并提示这是由于三维结构分析导致突变的CD155与dNaM-1亲和力降低所致。然而，出乎意料的是，我们发现该突变增加了与TIGIT的结合亲和力，而不是降低了与dNaM-1的结合亲和力，并诱导了比WT CD155更强的信号。我们的结果表明，该突变通过在肿瘤微环境中的免疫细胞中产生更强的抑制信号来抑制肿瘤免疫反应。我们发现CD155突变(Ala67Thr)增加了与抑制性免疫受体TIGIT的结合亲和力，并诱导了比野生型CD155更强的信号。我们的结果表明，该突变通过在肿瘤微环境中的免疫细胞中产生更强的抑制信号来抑制肿瘤免疫反应。
CD155 is a shared ligand for activating and inhibitory immunoreceptors DNAX accessory molecule 1 (DNAM‐1), also called CD226, and T cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT), which are expressed on natural killer (NK) cells and T cells, and positively and negatively regulates tumor immune responses, respectively. A recent study showed that the single nucleotide polymorphism rs1058402G>A causing a mutation to Thr from Ala at residue 67 of CD155 is associated with worse overall survival of patients with small cell lung cancer and suggested that this is caused by the decreased affinity of mutant CD155 for DNAM‐1 as a result of the 3D structural analysis. Unexpectedly, however, we found that the mutation increased the binding affinity for TIGIT rather than decreased the binding affinity for DNAM‐1 and induced a stronger signal than WT CD155. Our results suggest that the mutation suppresses tumor immune responses by generating a stronger inhibitory signal in immune cells in the tumor microenvironment. We found that CD155 mutation (Ala67Thr) increased the binding affinity for an inhibitory immunoreceptor TIGIT and induced a stronger signal than wild‐type CD155. Our results suggest that the mutation suppresses tumor immune responses by generating a stronger inhibitory signal in immune cells in the tumor microenvironment.
登录
查看更多内容
影响因子：
7.3
作者：
Ge Z;Peppelenbosch MP;Sprengers D;Kwekkeboom J
通讯作者：
Kwekkeboom J
影响因子：
5.6
作者：
Sun, Yu;Luo, Jiping;Ke, Zunfu
通讯作者：
Ke, Zunfu
影响因子：
64.5
作者：
MENDELSOHN, CL;WIMMER, E;RACANIELLO, VR
通讯作者：
RACANIELLO, VR
影响因子：
15.3
作者：
Okumura, Genki;Iguchi-Manaka, Akiko;Shibuya, Kazuko
通讯作者：
Shibuya, Kazuko
影响因子：
30.5
作者：
Yu, Xin;Harden, Kristin;Grogan, Jane L.
通讯作者：
Grogan, Jane L.