不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Sting Is Commonly and Differentially Expressed in T- and Nk-Cell but Not B-Cell Non-Hodgkin Lymphomas.
Sting Is Commonly and Differentially Expressed in T- and Nk-Cell but Not B-Cell Non-Hodgkin Lymphomas.
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本研究在158例T细胞和自然杀伤(NK)细胞非霍奇金淋巴瘤(NHL)、265例B细胞NHL,以及反应性淋巴结和扁桃体对照样本中,调查干扰素基因刺激因子(STING)的表达模式。采用治疗前诊断性活检标本进行免疫组化评估STING表达。以任意设定的10%为截断值,T/NK细胞NHL中STING表达存在差异:间变性淋巴瘤激酶阳性间变性大细胞淋巴瘤(ALK+ ALCL)38例中36例阳性(95%);ALK阴性ALCL 37例中23例(62%);血管免疫母细胞性T细胞淋巴瘤13例中1例(7.7%);非特指型外周T细胞淋巴瘤19例中15例(79%);鼻型结外NK/T细胞淋巴瘤36例中20例(56%);T细胞淋巴母细胞淋巴瘤7例中6例(86%);蕈样肉芽肿4例中3例(75%)。T/NK细胞淋巴瘤患者中,STING表达与临床病理参数或结局无关。相比之下,全部265例不同类型B细胞NHL均为STING阴性。
此外,6/7种T细胞NHL细胞系(包括ALK阳性和阴性ALCL细胞系)STING mRNA水平均很高,而7种B细胞NHL细胞系中的表达极低或检测不到,提示肿瘤性B细胞中STING发生转录下调。采用Western blot和细胞块免疫组化检测蛋白水平时,STING表达仅限于T细胞NHL细胞系。
综上,STING可作为T/NK细胞淋巴瘤的新型生物标志物和治疗靶点;cGAS-STING活性调节剂已可用于临床,因此具有直接的免疫治疗意义。
The expression patterns of stimulator of interferon genes (STING) were investigated in a cohort of 158 T- and natural killer (NK)-cell and 265 B-cell non-Hodgkin lymphomas (NHLs), as well as in control reactive lymph nodes and tonsils. STING expression was assessed by immunohistochemical methods using diagnostic biopsy specimens obtained prior to treatment. Using an arbitrary 10% cutoff, STING was differentially expressed among T/NK-cell NHLs; positive in 36 out of 38 (95%) cases of ALK+ anaplastic large cell lymphoma (ALCL), 23 out of 37 (62%) ALK-ALCLs, 1 out of 13 (7.
7%) angioimmunoblastic T-cell lymphomas, 15 out of 19 (79%) peripheral T-cell lymphomas, not otherwise specified, 20 out of 36 (56%) extranodal NK/T-cell lymphomas of nasal type, 6 out of 7 (86%) T-cell lymphoblastic lymphomas, and 3 out of 4 (75%) mycosis fungoides. STING expression did not correlate with clinicopathological parameters or outcome in these patients with T/NK-cell lymphoma. By contrast, all 265 B-cell NHLs of various types were STING-negative.
In addition, STING mRNA levels were very high in 6 out of 7 T-cell NHL cell lines, namely, ALK+ and ALK-ALCL cell lines, and very low or undetectable in 7 B-cell NHL cell lines, suggesting transcriptional downregulation of STING in neoplastic B-cells.
At the protein level, using Western blot analysis and immunohistochemistry performed on cell blocks, STING expression was found to be restricted to T-cell NHL cell lines. Taken together, STING expression represents a novel biomarker and therapeutic target in T- and NK-cell lymphomas with direct immunotherapeutic implications since modulators of cGAS-STING activity are already available for clinical use.
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