Combined chemoradiotherapy and programmed cell death-ligand 1 blockade leads to changes in the circulating T-cell receptor repertoire of patients with non-small-cell lung cancer.
Combined chemoradiotherapy and programmed cell death-ligand 1 blockade leads to changes in the circulating T-cell receptor repertoire of patients with non-small-cell lung cancer.
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作者：
联合放化疗（CRT）和程序性细胞死亡配体1（PD-L1）阻断是不可切除的III期非小细胞肺癌（NSCLC）的新护理标准。虽然这种巩固治疗提高了NSCLC患者的总生存率，但CRT和免疫治疗对T细胞的协同作用机制仍不清楚。此外，缺乏可靠的生物标志物来预测对治疗的临床反应。在这项研究中，我们分析了5例NSCLC患者外周血中的T细胞受体（TCR）序列。在治疗前、CRT后和PD-L1阻断后进行T细胞受体分析。值得注意的是，我们在所有完全缓解的病例中观察到优势T细胞克隆型的扩增和改变。相比之下，在疾病进展的病例中既没有观察到TCR库的扩增也没有观察到TCR库的改变。T细胞扩增在CRT后开始，并在PD-L1阻断后进一步增强。我们的研究结果表明，CRT对循环T细胞的全身效应，除了对有限的肿瘤部位的疗效。循环T细胞克隆型的动态变化可能对联合CRT和PD-L1阻滞具有预后意义。本研究分析了联合放化疗和PD-L1阻断前后NSCLC患者外周血中的TCR序列。分析发现，在完全缓解的病例中，优势T细胞克隆型扩增。这些发现表明CRT对循环T细胞的全身效应，这可能具有预后意义。
Combined chemoradiotherapy (CRT) and programmed cell death‐ligand 1 (PD‐L1) blockade is a new care standard for unresectable stage III non‐small‐cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy. In this study, we analyzed T‐cell receptor (TCR) sequences in the peripheral blood of five patients with NSCLC. T‐cell receptor analysis was undertaken before treatment, after CRT, and after PD‐L1 blockade. Notably, we observed the expansion and alteration of the dominant T‐cell clonotypes in all cases with a complete response. In contrast, neither expansion nor alteration of the TCR repertoire was observed in cases with progressive disease. T cell expansion was initiated after CRT and was further enhanced after PD‐L1 blockade. Our findings suggest the systemic effect of CRT on circulating T cells in addition to the curative effect on limited tumor sites. Dynamic changes in circulating T‐cell clonotypes could have a prognostic significance for combined CRT and PD‐L1 blockade. This study analyzed TCR sequences in the peripheral blood of patients with NSCLC before and after combined chemoradiotherapy and PD‐L1 blockade. The analysis found the expansion of the dominant T‐cell clonotypes in the cases with a complete response. These findings suggest the systemic effect of CRT on circulating T cells, which may have a prognostic significance.
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DOI：
10.1073/pnas.2102611118
发表时间：
2021-06-15
影响因子：
11.1
作者：
Lussier，Danielle M.;Alspach，Elise;Schreiber，Robert D.
通讯作者：
Schreiber，Robert D.
影响因子：
82.9
作者：
Formenti SC;Rudqvist NP;Golden E;Cooper B;Wennerberg E;Lhuillier C;Vanpouille-Box C;Friedman K;Ferrari de Andrade L;Wucherpfennig KW;Heguy A;Imai N;Gnjatic S;Emerson RO;Zhou XK;Zhang T;Chachoua A;Demaria S
通讯作者：
Demaria S
影响因子：
64.8
作者：
Twyman-Saint Victor, Christina;Rech, Andrew J.;Maity, Amit;Rengan, Ramesh;Pauken, Kristen E.;Stelekati, Erietta;Benci, Joseph L.;Xu, Bihui;Dada, Hannah;Odorizzi, Pamela M.;Herati, Ramin S.;Mansfield, Kathleen D.;Patsch, Dana;Amaravadi, Ravi K.;Schuchter, Lynn M.;Ishwaran, Hemant;Mick, Rosemarie;Pryma, Daniel A.;Xu, Xiaowei;Feldman, Michael D.;Gangadhar, Tara C.;Hahn, Stephen M.;Wherry, E. John;Vonderheide, Robert H.;Minn, Andy J.
通讯作者：
Minn, Andy J.
太平洋试验的五年生存结果：在III期非小细胞肺癌中进行化学放录后的杜瓦卢马布。
DOI：
10.1200/jco.21.01308
发表时间：
2022-04-20
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Spigel DR;Faivre-Finn C;Gray JE;Vicente D;Planchard D;Paz-Ares L;Vansteenkiste JF;Garassino MC;Hui R;Quantin X;Rimner A;Wu YL;Özgüroğlu M;Lee KH;Kato T;de Wit M;Kurata T;Reck M;Cho BC;Senan S;Naidoo J;Mann H;Newton M;Thiyagarajah P;Antonia SJ
通讯作者：
Antonia SJ
影响因子：
8
作者：
Hirama T;Tokita S;Nakatsugawa M;Murata K;Nannya Y;Matsuo K;Inoko H;Hirohashi Y;Hashimoto S;Ogawa S;Takemasa I;Sato N;Hata F;Kanaseki T;Torigoe T
通讯作者：
Torigoe T