Integrative tumour mutation burden with CD39 and PD-L1 for the prediction of response to PD-L1 blockade and adjuvant chemotherapy in muscle-invasive bladder cancer patients.
Integrative tumour mutation burden with CD39 and PD-L1 for the prediction of response to PD-L1 blockade and adjuvant chemotherapy in muscle-invasive bladder cancer patients.
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CD39 和 PD-L1 的综合肿瘤突变负荷用于预测肌层浸润性膀胱癌患者对 PD-L1 阻断和辅助化疗的反应
DOI：
10.1038/s41416-022-01943-y
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发表时间：
2022-11
影响因子：
8.8
通讯作者：
Zhang, Weijuan
中科院分区：
文献类型：
--
作者：
Liu, Chunnan;Liu, Zhaopei;Jin, Kaifeng;Zeng, Han;Shao, Fei;Chang, Yuan;Wang, Yiwei;Xu, Le;Wang, Zewei;Zhu, Yu;Zhang, Weijuan
CD39是一种将细胞外ATP （eATP）转化为腺苷的限速酶，已被报道为免疫反应的关键调节剂，但其与治疗敏感性的相关性尚不清楚。我们进行了这项研究，以确定CD39和传统生物标志物的整合是否可以提高对PD-L1阻断和铂基化疗反应性的预测。本研究回顾性纳入IMvigor210试验、TCGA数据库和中山医院共760例患者。我们构建了基于CD39、PD-L1和肿瘤突变负荷（TMB）的CPT评分系统，并验证了其在预测MIBC患者治疗反应性方面的有效性。应用Kaplan-Meier生存期和Cox回归分析评估患者的临床结局。CPT评分系统可以预测PD-L1阻断和铂基化疗的反应。CPT评分与APOBEC突变特征、SNV新抗原富集、抗原呈递和TCR信号传导呈正相关。高CPT评分也表明炎症免疫表型和基底/鳞状分子亚型。CD39表达与MIBC的免疫原性背景密切相关。将CD39与PD-L1和TMB结合，可以对MIBC患者对PD-L1阻断和铂类化疗的敏感性进行分层。
CD39, a rate-limiting enzyme to convert extracellular ATP (eATP) to adenosine, has been reported to be a key modulator of immune response, but its correlation with therapeutic sensitivity remains obscure. We conducted this study to determine whether the integration of CD39 and traditional biomarkers could improve the prediction of responsiveness to PD-L1 blockade and platinum-based chemotherapy. We retrospectively enrolled a total of 760 patients from IMvigor210 trial, TCGA database and Zhongshan Hospital in this study. We constructed the CPT scoring system based on CD39, PD-L1 and tumour mutation burden (TMB) and validated its efficacy in predicting therapeutic responsiveness in MIBC patients. Kaplan–Meier survival and Cox regression analyses were applied to assess clinical outcomes of patients. The CPT scoring system could predict the response to PD-L1 blockade and platinum-based chemotherapy. The CPT score was positively correlated with APOBEC mutational signature and SNV neoantigens enrichment, antigen presentation, and TCR signalling. High CPT score also indicated the inflamed immune phenotype and basal/squamous molecular subtype. CD39 expression is closely correlated with the immunogenic contexture of MIBC. Integrating CD39 with PD-L1 and TMB could stratify the sensitivity of patients with MIBC to PD-L1 blockade and platinum-based chemotherapy.
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影响因子：
64.5
作者：
Litchfield K;Reading JL;Puttick C;Thakkar K;Abbosh C;Bentham R;Watkins TBK;Rosenthal R;Biswas D;Rowan A;Lim E;Al Bakir M;Turati V;Guerra-Assunção JA;Conde L;Furness AJS;Saini SK;Hadrup SR;Herrero J;Lee SH;Van Loo P;Enver T;Larkin J;Hellmann MD;Turajlic S;Quezada SA;McGranahan N;Swanton C
通讯作者：
Swanton C
影响因子：
30.5
作者：
Finkin S;Yuan D;Stein I;Taniguchi K;Weber A;Unger K;Browning JL;Goossens N;Nakagawa S;Gunasekaran G;Schwartz ME;Kobayashi M;Kumada H;Berger M;Pappo O;Rajewsky K;Hoshida Y;Karin M;Heikenwalder M;Ben-Neriah Y;Pikarsky E
通讯作者：
Pikarsky E
影响因子：
8
作者：
Feng, Daofu;Qin, Bo;Sinicrope, Frank A.
通讯作者：
Sinicrope, Frank A.
影响因子：
25.7
作者：
Calderaro, Julien;Petitprez, Florent;Sautes-Fridman, Catherine
通讯作者：
Sautes-Fridman, Catherine
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T