IL-5-producing CD4+ T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer

被引：129

作者：

Blomberg, Olga S. ^{[1
,2
,3
]}

Spagnuolo, Lorenzo ^{[1
,2
]}

Garner, Hannah ^{[1
,2
]}

Voorwerk, Leonie ^{[1
]}

Isaeva, Olga I. ^{[1
,4
]}

van Dyk, Ewald ^{[1
,2
,4
]}

Bakker, Noor ^{[1
,2
]}

Chalabi, Myriam ^{[5
,6
,7
]}

Klaver, Chris ^{[1
]}

Duijst, Maxime ^{[1
]}

Kersten, Kelly ^{[1
,11
]}

Bruggemann, Marieke ^{[1
]}

Pastoors, Dorien ^{[1
,2
,12
]}

Hau, Cheei-Sing ^{[1
,2
]}

Vrijland, Kim ^{[1
,2
]}

Raeven, Elisabeth A. M. ^{[1
,2
]}

Kaldenbach, Daphne ^{[1
]}

Kos, Kevin ^{[1
,2
,3
]}

Afonina, Inna S. ^{[8
,9
]}

Kaptein, Paulien ^{[5
]}

Hoes, Louisa ^{[5
]}

Theelen, Willemijn S. M. E. ^{[10
]}

Baas, Paul ^{[10
]}

Voest, Emile E. ^{[5
,7
]}

Beyaert, Rudi ^{[8
,9
]}

Thommen, Daniela S. ^{[5
]}

Wessels, Lodewyk F. A. ^{[4
]}

de Visser, Karin E. ^{[1
,2
,3
]}

Kok, Marleen ^{[1
,7
]}

机构：

[1] Netherlands Canc Inst, Div Tumor Biol Immunol, Amsterdam, Netherlands

[2] Oncode Inst, Utrecht, Netherlands

[3] Leiden Univ, Med Ctr, Dept Immunol, Leiden, Netherlands

[4] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands

[5] Netherlands Canc Inst, Div Mol Oncol Immunol, Amsterdam, Netherlands

[6] Netherlands Canc Inst, Dept Gastrointestinal Oncol, Amsterdam, Netherlands

[7] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands

[8] Univ Ghent, VIB UGent Ctr Inflammat Res, Ghent, Belgium

[9] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium

[10] Netherlands Canc Inst, Dept Thorac Oncol, Amsterdam, Netherlands

[11] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA

[12] Erasmus MC, Dept Hematol, Rotterdam, Netherlands

来源：

CANCER CELL | 2023年 / 41卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

SIGLEC-F; RNA-SEQ; MICE; METASTASIS; LYMPHOCYTE; CISPLATIN; BLOOD; IL-33; IDENTIFICATION; PEMBROLIZUMAB;

D O I：

10.1016/j.ccell.2022.11.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Immune checkpoint blockade (ICB) has heralded a new era in cancer therapy. Research into the mechanisms underlying response to ICB has predominantly focused on T cells; however, effective immune responses require tightly regulated crosstalk between innate and adaptive immune cells. Here, we combine unbiased analysis of blood and tumors from metastatic breast cancer patients treated with ICB with mechanistic studies in mouse models of breast cancer. We observe an increase in systemic and intratumoral eosinophils in patients and mice responding to ICB treatment. Mechanistically, ICB increased IL-5 production by CD4(+) T cells, stimulating elevated eosinophil production from the bone marrow, leading to systemic eosinophil expansion. Additional induction of IL-33 by ICB-cisplatin combination or recombinant IL-33 promotes intratumoral eosinophil infiltration and eosinophil-dependent CD8(+) T cell activation to enhance ICB response. This work demonstrates the critical role of eosinophils in ICB response and provides proof-of-principle for eosinophil engagement to enhance ICB efficacy.

引用

页码：106 / +

页数：29

共 100 条

[11] Tumor-Derived IL33 Promotes Tissue-Resident CD8+ T Cells and Is Required for Checkpoint Blockade Tumor Immunotherapy [J].