A neutrophil response linked to tumor control in immunotherapy

被引：225

作者：

Gungabeesoon, Jeremy ^{[1
,2
]}

Gort-Freitas, Nicolas A. ^{[3
]}

Kiss, Mate ^{[4
,5
]}

Bolli, Evangelia ^{[3
,4
,5
]}

Messemaker, Marius ^{[1
,2
,6
]}

Siwicki, Marie ^{[1
,2
]}

Hicham, Mehdi ^{[4
,5
]}

Bill, Ruben ^{[3
,4
,5
]}

Koch, Peter ^{[1
,2
]}

Cianciaruso, Chiara ^{[3
,4
,5
]}

Duval, Florent ^{[4
,5
]}

Pfirschke, Christina ^{[1
,2
]}

Mazzola, Michael ^{[7
]}

Peters, Solange ^{[8
,9
]}

Homicsko, Krisztian ^{[5
,10
,11
,12
]}

Garris, Christopher ^{[1
,2
]}

Weissleder, Ralph ^{[1
,2
,3
]}

Klein, Allon M. ^{[3
]}

Pittet, Mikael J. ^{[1
,2
,4
,5
,10
,12
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Syst Biol, Res Inst, Boston, MA 02114 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA

[4] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland

[5] AGORA Canc Res Ctr, Lausanne, Switzerland

[6] Netherlands Canc Inst, Div Mol Oncol & Immunol, Amsterdam, Netherlands

[7] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA

[8] CHU Vaudois, Dept Oncol, Serv Med Oncol, Lausanne, Switzerland

[9] Univ Lausanne, Dept Oncol, Lausanne, Switzerland

[10] Ludwig Inst Canc Res, Lausanne, Switzerland

[11] CHU Vaudois, Dept Oncol, Lausanne, Switzerland

[12] Swiss Canc Ctr Leman, Lausanne, Switzerland

来源：

CELL | 2023年 / 186卷 / 07期

基金：

瑞士国家科学基金会;

关键词：

LUNG-CANCER; PRESENTING CELLS; T-CELLS; BLOCKADE; CXCR3;

D O I：

10.1016/j.cell.2023.02.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neutrophils accumulate in solid tumors, and their abundance correlates with poor prognosis. Neutrophils are not homogeneous, however, and could play different roles in cancer therapy. Here, we investigate the role of neutrophils in immunotherapy, leading to tumor control. We show that successful therapies acutely expanded tumor neutrophil numbers. This expansion could be attributed to a Sellhi state rather than to other neutrophils that accelerate tumor progression. Therapy-elicited neutrophils acquired an interferon gene signature, also seen in human patients, and appeared essential for successful therapy, as loss of the inter-feron-responsive transcription factor IRF1 in neutrophils led to failure of immunotherapy. The neutrophil response depended on key components of anti-tumor immunity, including BATF3-dependent DCs, IL-12, and IFNg. In addition, we found that a therapy-elicited systemic neutrophil response positively correlated with disease outcome in lung cancer patients. Thus, we establish a crucial role of a neutrophil state in medi-ating effective cancer therapy.

引用

页码：1448 / 1464.e20

页数：38

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