Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma.
Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma.
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DOI：
10.1038/s41467-022-29342-0
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发表时间：
2022-04-11
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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CD8+T细胞对肿瘤突变来源的新抗原的反应性被广泛认为有助于免疫检查点阻断(ICB)诱导的抗肿瘤免疫。在这里，我们表明，在接受PD-L1-阻滞剂治疗的转移性尿路上皮癌(MUC)中，新抗原反应性CD8+T细胞(NART)数量在治疗前到治疗后3周之间的扩大，区分了转移性尿路上皮癌(MUC)受控患者和进展性疾病患者。来自临床试验NCT02108652的24名患者对由DNA条形码标记的pMHC多聚体组成的患者特异性新肽库的外周CD8+T细胞识别的纵向分析还表明，来自疾病控制患者的外周NART具有PD1+Ki67+效应表型的特征，与旁观者大量和病毒抗原反应性CD8+T细胞相比，CD39水平升高。这项研究提供了对ICB后NART特征的见解，并表明MUC患者早期NART的扩张和激活与ICB的反应有关。免疫检查点阻断疗法在高比例的癌症患者中取得了成功，但其他人仍然没有反应。作者指出，通过对转移性膀胱癌患者外周血中早期肿瘤抗原特异性CD8 T细胞反应的纵向分析，转移性膀胱癌的治疗成功是可以预测的。
CD8+ T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in the number of neoantigen-reactive CD8+ T cell (NART) populations between pre-treatment to 3-weeks post-treatment distinguishes patients with controlled disease compared to patients with progressive disease in metastatic urothelial carcinoma (mUC) treated with PD-L1-blockade. The longitudinal analysis of peripheral CD8+ T cell recognition of patient-specific neopeptide libraries consisting of DNA barcode-labelled pMHC multimers in a cohort of 24 patients from the clinical trial NCT02108652 also shows that peripheral NARTs derived from patients with disease control are characterised by a PD1+ Ki67+ effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8+ T cells. The study provides insights into NART characteristics following ICB and suggests that early-stage NART expansion and activation are associated with response to ICB in patients with mUC. Immune checkpoint blockade therapy is successful in a high proportion of cancer patients, but others remain unresponsive. Authors here show that therapeutic success might be predictable in metastatic bladder cancer by longitudinal analysis of the early neoantigen-specific CD8 T cell response in peripheral blood.
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DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
影响因子：
7.3
作者：
Bjerregaard AM;Nielsen M;Jurtz V;Barra CM;Hadrup SR;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
影响因子：
22.7
作者：
Ghorani, Ehsan;Reading, James L.;Quezada, Sergio A.
通讯作者：
Quezada, Sergio A.
DOI：
10.1126/science.aar3593
发表时间：
2018-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cristescu R;Mogg R;Ayers M;Albright A;Murphy E;Yearley J;Sher X;Liu XQ;Lu H;Nebozhyn M;Zhang C;Lunceford JK;Joe A;Cheng J;Webber AL;Ibrahim N;Plimack ER;Ott PA;Seiwert TY;Ribas A;McClanahan TK;Tomassini JE;Loboda A;Kaufman D
通讯作者：
Kaufman D
影响因子：
3.8
作者：
Engqvist, Hanna;Parris, Toshima Z.;Helou, Khalil
通讯作者：
Helou, Khalil