Neoantigen reactive T cells correlate with the low mutational burden in hematological malignancies.
Neoantigen reactive T cells correlate with the low mutational burden in hematological malignancies.
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DOI：
10.1038/s41375-022-01705-y
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发表时间：
2022-11
期刊：
影响因子：
11.4
通讯作者：
Hadrup, Sine Reker
中科院分区：
文献类型：
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作者：
Saini, Sunil Kumar;Holmberg-Thyden, Staffan;Bjerregaard, Anne-Mette;Unnikrishnan, Ashwin;Dorfmuller, Simon;Platzbecker, Uwe;Tirado-Gonzalez, Irene;Boenig, Halvard;El Fassi, Daniel;Gronbaek, Kirsten;Pimanda, John;Medyouf, Hind;Hadrup, Sine Reker
我们在此报告了MDS患者骨髓中新表位T细胞识别的离体检测。我们的研究是第一个报告可以在MDS患者中检测到功能性新抗原特异性T细胞的研究之一，这表明尽管MDS的突变负荷较低，但T细胞可以识别突变衍生的抗原。在这项研究中鉴定的两种识别T细胞的新抗原都来自于骨髓肿瘤中一种特征良好的驱动基因（RUNX1;患者DD 30）和AP 3S 1基因突变（患者DD 31），其在发病机制中的作用未知，这表明新抗原可以由这种恶性肿瘤中的驱动突变和乘客突变产生。在13名患者中的2名中检测到的新表位反应性T细胞的水平低于高突变负荷癌症中的类似评估。最近在黑色素瘤和膀胱癌中的一项研究证明了在用免疫疗法治疗之前，18名黑色素瘤患者中的13名和24名膀胱癌患者中的18名中的新表位T细胞识别[9，10]。我们的数据代表了一个相对较小的患者队列，尽管存在这种限制，但本文提供的研究结果支持了早期的观点，即发现新抗原反应性T细胞群的机会与肿瘤的突变负荷相关（图1 GI）[11]。这项研究中发现的特异性T细胞的低频率可能对MDS患者免疫治疗的发展有影响。例如，旨在刺激T细胞靶向恶性造血干细胞的疗法可能无法依赖新表位来驱动免疫应答，而新表位已被认为是高突变负荷疾病中检查点抑制的主要作用机制[4]。
DISCUSSIONWe here report the ex-vivo detection of neoepitope T cell recognition in the bone marrow of MDS patients. Our study is among the first to report that functional neoantigen-specific T cells can be detected in MDS patients, demonstrating that despite the low-mutational burden in MDS, T cell recognition of mutation-derived antigens can occur. The two neoantigens recognizing T cells identified in this study resulted both from a well-characterized driver gene in myeloid neoplasms (RUNX1; patient DD30) and from a mutation in AP3S1 gene (patient DD31) not known for its role in pathogenesis, which suggests that neoantigens can arise from both driven and passenger mutations in this malignancy.The level of recognition observed here, ie, neoepitope-reactive T cells detected in two out of 13 patients, is lower than similar evaluations in high mutational burden cancer. A recent study in melanoma and bladder cancer demonstrated neoepitope T cell recognition in 13 out of 18 melanoma patients and 18 of 24 patients with bladder cancer before treatment with immunotherapy [9, 10]. Our data represents a relatively small patient cohort, despite this limitation, the findings presented here support the earlier notion that the chance of finding a neoantigen-reactive T cell population correlates to the mutational burden of the tumor (Fig. 1 GI)[11]. The low frequency of specific T cells found in this study could have implications for the development of immunotherapy in MDS patients. For example, therapies intended to stimulate T cells to target malignant hematopoietic stem cells might not be able to rely on neoepitopes to drive the immune response, which has been recognized as the primary mechanism of action for checkpoint inhibition in diseases with a high mutational burden [4].
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DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
4.5
作者：
Tanaka, Tiffany N.;Ferrari, Valentina;Bejar, Rafael
通讯作者：
Bejar, Rafael
影响因子：
4.5
作者：
Ferrari, Valentina;Tarke, Alison;Vitiello, Antonella
通讯作者：
Vitiello, Antonella
影响因子：
20.3
作者：
Greenberg, Peter L.;Tuechler, Heinz;Haase, Detlef
通讯作者：
Haase, Detlef