Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1.
Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1.
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DOI：
10.1038/s41467-021-24293-4
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发表时间：
2021-06-29
影响因子：
16.6
通讯作者：
Heath JR
中科院分区：
文献类型：
--
作者：
Lu Y;Ng AHC;Chow FE;Everson RG;Helmink BA;Tetzlaff MT;Thakur R;Wargo JA;Cloughesy TF;Prins RM;Heath JR
由于患者间和肿瘤内的异质性，复发性多形性胶质母细胞瘤患者对新辅助免疫检查点阻断的反应一直难以解释。我们报告了对复发性胶质母细胞瘤和高风险黑色素瘤患者的肿瘤组织进行的比较分析，这两种患者都接受了新辅助检查点阻断治疗。我们开发了一个框架，该框架使用多重空间蛋白质分析，基于机器学习的图像分析和数据驱动的计算模型来研究肿瘤微环境中影响治疗反应的病理生理和分子因素。使用黑色素瘤来指导胶质母细胞瘤分析的解释，我们询问肿瘤的微观区室中的蛋白质表达，并确定细胞毒性CD 8 + T细胞、肿瘤生长、治疗反应和免疫细胞-细胞相互作用的相关性。这项工作揭示了胶质母细胞瘤和黑色素瘤之间的相似性，胶质母细胞瘤微环境特有的免疫抑制因子，以及增强新辅助免疫检查点阻断功效的潜在共同靶点。复发性多形性胶质母细胞瘤（GBM）患者对新辅助免疫检查点阻断（ICB）的反应一直难以解释。在这里，作者开发了一个肿瘤分析框架，揭示了GBM和黑色素瘤之间的分子相似性，以及GBM中免疫抑制的独特模式，表明新辅助ICB的潜在共同靶点。
The response of patients with recurrent glioblastoma multiforme to neoadjuvant immune checkpoint blockade has been challenging to interpret due to the inter-patient and intra-tumor heterogeneity. We report on a comparative analysis of tumor tissues collected from patients with recurrent glioblastoma and high-risk melanoma, both treated with neoadjuvant checkpoint blockade. We develop a framework that uses multiplex spatial protein profiling, machine learning-based image analysis, and data-driven computational models to investigate the pathophysiological and molecular factors within the tumor microenvironment that influence treatment response. Using melanoma to guide the interpretation of glioblastoma analyses, we interrogate the protein expression in microscopic compartments of tumors, and determine the correlates of cytotoxic CD8+ T cells, tumor growth, treatment response, and immune cell-cell interaction. This work reveals similarities shared between glioblastoma and melanoma, immunosuppressive factors that are unique to the glioblastoma microenvironment, and potential co-targets for enhancing the efficacy of neoadjuvant immune checkpoint blockade. The response to neoadjuvant immune checkpoint blockade (ICB) in patients with recurrent gliolastoma multiforme (GBM) has been challenging to interpret. Here the authors develop a tumor analysis framework that reveals molecular similarities between GBM and melanoma and unique patterns of immunosuppression in GBM indicating potential co-targets for neoadjuvant ICB.
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影响因子：
64.5
作者：
Goltsev Y;Samusik N;Kennedy-Darling J;Bhate S;Hale M;Vazquez G;Black S;Nolan GP
通讯作者：
Nolan GP
影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
3.8
作者：
Fox, Julie M.;Sage, Leo K.;Tripp, Ralph A.
通讯作者：
Tripp, Ralph A.
影响因子：
64.5
作者：
Liu Y;Yang M;Deng Y;Su G;Enninful A;Guo CC;Tebaldi T;Zhang D;Kim D;Bai Z;Norris E;Pan A;Li J;Xiao Y;Halene S;Fan R
通讯作者：
Fan R