Immunologic Features in De Novo and Recurrent Glioblastoma Are Associated with Survival Outcomes

被引：14

作者：

Alanio, Cecile ^{[1
,2
,3
,4
,5
,6
,13
]}

Blinder, Zev A. ^{[6
,7
,8
]}

Chang, Renee B. ^{[6
,8
,9
]}

Nasrallah, MacLean P. ^{[6
,10
]}

Delman, Devora ^{[6
,8
,9
]}

Li, Joey H. ^{[8
]}

Tang, Oliver Y. ^{[6
,11
]}

Zhang, Logan Y. ^{[6
,7
,8
]}

Zhang, Jiasi Vicky ^{[6
,7
,8
]}

Wherry, E. John ^{[3
,4
,5
,6
]}

Rourke, Donald M. O. ^{[6
,7
,8
]}

Beatty, Gregory L. ^{[6
,8
,9
,12
]}

机构：

[1] PSL Univ, Inst Curie, INSERM U932, Paris, France

[2] Inst Curie, Lab immunol Clin, Paris, France

[3] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA USA

[4] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA USA

[5] Parker Inst Canc Immunotherapy Univ Penn, Philadelphia, PA USA

[6] Univ Penn, Glioblastoma Translat Ctr Excellence, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA USA

[7] Univ Penn, Perelman Sch Med, Dept Neurosurg, Philadelphia, PA USA

[8] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA USA

[9] Univ Penn, Perelman Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA USA

[10] Univ Penn, Perelman Sch Med, Dept Pathol, Lab Med, Philadelphia, PA USA

[11] Warren Alpert Med Sch Brown Univ, Brown Univ, Providence, RI USA

[12] Univ Penn, Perelman Ctr Adv Med, South Pavil, Room 8-107,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA

[13] Hop 2eme Etage, Ctr Canc Immunotherapy, 26 Rue Ulm, F-75248 Paris 05, France

来源：

CANCER IMMUNOLOGY RESEARCH | 2022年 / 10卷 / 07期

关键词：

CD8(+) T-CELLS; STEM-CELLS; REVEALS; LANDSCAPE; SUBSETS; NICHE;

D O I：

10.1158/2326-6066.CIR-21-1050

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glioblastoma (GBM) is an immunologically "cold " tumor characterized by poor responsiveness to immunotherapy. Stan-dard of care for GBM is surgical resection followed by chemo-radiotherapy and maintenance chemotherapy. However, tumor recurrence is the norm, and recurring tumors are found fre-quently to have acquired molecular changes (e.g., mutations) that may influence their immunobiology. Here, we compared the immune contexture of de novo GBM and recurrent GBM (rGBM) using high-dimensional cytometry and multiplex IHC. Although myeloid and T cells were similarly abundant in de novo and rGBM, their spatial organization within tumors differed and was linked to outcomes. In rGBM, T cells were enriched and activated in perivascular regions and clustered with activated macrophages and fewer regulatory T cells. Moreover, a higher expression of phosphorylated STAT1 by T cells in these regions at recurrence was associated with a favorable prognosis. Together, our data identify differences in the immunobiology of de novo GBM and rGBM and identify perivascular T cells as potential therapeutic targets.

引用

页码：800 / 810

页数：11

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