Harnessing Natural Killer Cell Function for Genitourinary Cancers.
Harnessing Natural Killer Cell Function for Genitourinary Cancers.
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DOI：
10.1016/j.ucl.2020.07.002
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Sfakianos JP
中科院分区：
文献类型：
--
作者：
Bhardwaj N;Farkas AM;Gul Z;Sfakianos JP
自然杀伤细胞（NK细胞）是细胞毒性淋巴细胞，是先天免疫系统的成员。因此，它们缺乏T细胞和B细胞的抗原特异性，但可以识别下调人类白细胞抗原（HLA） I类和上调细胞应激标志物（如MICA、MICB、ULBP-1和脊髓灰质炎病毒受体）的细胞。由于ⅰ类应激配体的缺失和表达经常发生在病毒感染和癌症期间，NK细胞是抗病毒防御和肿瘤免疫监视的重要组成部分。nk细胞对潜在目标细胞的识别依赖于检测缺失自我的能力，正如克劳斯（klaus）最初提出的Kärre。在外周血、次级淋巴器官和组织的监测过程中，NK细胞上的杀伤性免疫球蛋白样受体（KIRs）识别由假定靶点表达的HLA-A、HLA-B和HLA-C。KIR与其同源的I类HLA分子结合，通过KIR细胞质结构域中ITIM（免疫受体酪氨酸基抑制基序）基序的磷酸化，向NK细胞传递抑制信号（图1，顶部）。随后SHP-1酪氨酸磷酸酶的募集导致NK细胞效应功能的抑制，并阻止NK细胞杀死靶标。然而，当NK细胞遇到I类HLA下调的病毒感染细胞或肿瘤细胞时，抑制KIR-HLA信号不传递。如果通过细胞应激配体与其同源的NK细胞上的激活受体的相互作用同时传递激活信号，则NK效应功能可以进行（见图1，底部）。
BackgroundNatural killer (NK cells) are cytotoxic lymphocytes that are members of the innate immune system. As such, they lack the antigen specificity of T and B cells but recognize cells that have downregulated human leukocyte antigen (HLA) class I and upregulated markers of cell stress, such as MICA, MICB, ULBP-1, and the polio virus receptor. Because loss of class I and expression of these stress ligands often occurs during viral infection and cancer, NK cells are important components of both antiviral defense and tumor immunosurveillance. NK-cell recognition of potential target cells relies on the ability to detect missing self, as initially proposed by Klause Kärre. 1 During surveillance in the peripheral blood, secondary lymphoid organs, and tissue, killer immunoglobulinlike receptors (KIRs) on NK cells recognize HLA-A, HLA-B, and HLA-C expressed by putative targets. Binding of the KIR to its cognate class I HLA molecule delivers an inhibitory signal to the NK cell via phosphorylation of ITIM (immunoreceptor tyrosine-based inhibitory motif) motifs in the KIR’s cytosolic domain (Fig. 1, top). Subsequent recruitment of the SHP-1 tyrosine phosphatase results in suppression of NK-cell effector function and prevents the NK cell from killing the target. However, when an NK cell encounters a virally infected cell or tumor cell that has downregulated class I HLA, the inhibitory KIR-HLA signal is not delivered. If there is a concurrent, activating signal delivered through interaction of a cell stress ligand with its cognate, activating receptor on the NK cell, then NK effector functions can proceed (see Fig. 1, bottom).
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DOI：
10.1111/j.1464-410x.1994.tb07635.x
发表时间：
1994-05-01
期刊：
BRITISH JOURNAL OF UROLOGY
影响因子：
--
作者：
CHRISTMAS, TJ
通讯作者：
CHRISTMAS, TJ
影响因子：
7.3
作者：
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通讯作者：
Vales-Gomez, Mar
影响因子：
3.7
作者：
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通讯作者：
Wikström P
DOI：
10.1016/j.clim.2014.10.005
发表时间：
2014-12
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
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通讯作者：
Netea MG
影响因子：
3.7
作者：
Koo KC;Shim DH;Yang CM;Lee SB;Kim SM;Shin TY;Kim KH;Yoon HG;Rha KH;Lee JM;Hong SJ
通讯作者：
Hong SJ