B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

被引：284

作者：

Griss, Johannes ^{[1
,2
]}

Bauer, Wolfgang ^{[1
]}

Wagner, Christine ^{[1
]}

Simon, Martin ^{[1
]}

Chen, Minyi ^{[1
]}

Grabmeier-Pfistershammer, Katharina ^{[1
,3
]}

Maurer-Granofszky, Margarita ^{[1
,13
]}

Roka, Florian ^{[1
]}

Penz, Thomas ^{[4
]}

Bock, Christoph ^{[4
,5
]}

Zhang, Gao ^{[6
,7
,14
,15
]}

Herlyn, Meenhard ^{[6
,7
]}

Glatz, Katharina ^{[8
]}

Laubli, Heinz ^{[9
]}

Mertz, Kirsten D. ^{[10
]}

Petzelbauer, Peter ^{[1
]}

Wiesner, Thomas ^{[1
]}

Hartl, Markus ^{[11
]}

Pickl, Winfried F. ^{[12
]}

Somasundaram, Rajasekharan ^{[6
,7
]}

Steinberger, Peter ^{[3
]}

Wagner, Stephan N. ^{[1
]}

机构：

[1] Med Univ Vienna, Dept Dermatol, A-1090 Vienna, Austria

[2] EMBL European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England

[3] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Inst Immunol, A-1090 Vienna, Austria

[4] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria

[5] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria

[6] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA

[7] Wistar Inst Anat & Biol, Melanoma Res Ctr, Philadelphia, PA 19104 USA

[8] Univ Hosp Basel, Inst Pathol, CH-4031 Basel, Switzerland

[9] Univ Hosp Basel, Div Med Oncol, CH-4031 Basel, Switzerland

[10] Cantonal Hosp Baselland, Inst Pathol, CH-4410 Liestal, Switzerland

[11] Univ Vienna, Vienna BioCtr VBC, MFPL, Mass Spectrometry Facil, A-1030 Vienna, Austria

[12] Med Univ Vienna, Div Cellular Immunol & Immunohematol, Inst Immunol, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria

[13] Childrens Canc Res Inst, A-1090 Vienna, Austria

[14] Duke Univ, Med Ctr, Dept Neurosurg, Durham, NC 27710 USA

[15] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

奥地利科学基金会; 欧盟地平线“2020”;

关键词：

TERTIARY LYMPHOID STRUCTURES; CD8(+) T-CELLS; PROGNOSTIC-SIGNIFICANCE; SAMPLE PREPARATION; PLASMA-CELLS; LOW NUMBER; CANCER; LYMPHOCYTES; EXPRESSION; CARCINOMA;

D O I：

10.1038/s41467-019-12160-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Current theories on regulation of inflammation center on anti-tumor T cell responses. Here we show that tumor associated B cells are vital to melanoma associated inflammation. Human B cells express pro- and anti-inflammatory factors and differentiate into plasmablast-like cells when exposed to autologous melanoma secretomes in vitro. This plasmablast-like phenotype can be reconciled in human melanomas where plasmablast-like cells also express T cell-recruiting chemokines CCL3, CCL4, CCL5. Depletion of B cells in melanoma patients by anti-CD20 immunotherapy decreases tumor associated inflammation and CD8(+) T cell numbers. Plasmablast-like cells also increase PD-1(+) T cell activation through anti-PD-1 blockade in vitro and their frequency in pretherapy melanomas predicts response and survival to immune checkpoint blockade. Tumor associated B cells therefore orchestrate and sustain melanoma inflammation and may represent a predictor for survival and response to immune checkpoint blockade therapy.

引用

页数：14

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