Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

被引：98

作者：

Horeweg, Nanda ^{[1
]}

Workel, Hagma H. ^{[2
]}

Loiero, Dominik ^{[3
]}

Church, David N. ^{[4
,5
]}

Vermij, Lisa ^{[6
]}

Leon-Castillo, Alicia ^{[6
]}

Krog, Ricki T. ^{[6
,7
]}

de Boer, Stephanie M. ^{[1
]}

Nout, Remi A. ^{[8
]}

Powell, Melanie E. ^{[9
]}

Mileshkin, Linda R. ^{[10
]}

MacKay, Helen ^{[11
]}

Leary, Alexandra ^{[12
]}

Singh, Naveena ^{[13
]}

Juergenliemk-Schulz, Ina M. ^{[14
]}

Smit, Vincent T. H. B. M. ^{[6
]}

Creutzberg, Carien L. ^{[1
]}

Koelzer, Viktor H. ^{[3
,15
,16
]}

Nijman, Hans W. ^{[2
]}

Bosse, Tjalling ^{[6
]}

de Bruyn, Marco ^{[2
]}

机构：

[1] Leiden Univ, Dept Radiat Oncol, Med Ctr, Leiden, Netherlands

[2] Univ Med Ctr Groningen, Dept Gynaecol Oncol, Groningen, Netherlands

[3] Univ Zurich, Univ Hosp Zurich, Dept Pathol & Mol Pathol, Zurich, Switzerland

[4] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[5] Oxford Univ Hosp NHS Fdn Trust, Oxford NIHR Comprehens Biomed Res Ctr, Oxford, England

[6] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands

[7] Leiden Univ, Dept Surg, Med Ctr, Leiden, Netherlands

[8] Erasmus MC, Dept Radiotherapy, Canc Inst, Rotterdam, Netherlands

[9] Barts Hlth NHS Trust, Dept Clin Oncol, London, England

[10] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia

[11] Sunnybrook Odette Canc Ctr, Div Med Oncol & Hematol, Toronto, ON, Canada

[12] Gustave Roussy, Dept Med Oncol, Villejuif, France

[13] Barts Hlth NHS Trust, Dept Pathol, London, England

[14] Univ Med Ctr Utrecht, Dept Radiat Oncol, Utrecht, Netherlands

[15] Univ Oxford, Dept Oncol, Oxford, England

[16] Univ Oxford, Nuffield Dept Med, Oxford, England

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

英国惠康基金;

关键词：

B-CELLS; IMMUNOTHERAPY; CLUSTERPROFILER; RESPONSES; SURVIVAL;

D O I：

10.1038/s41467-022-29040-x

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：

B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naive B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis shows association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence show L1CAM expression in mature TLS, independent of L1CAM expression in the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank are evaluated, TLS are found in 19%. L1CAM expressing TLS are most common in mismatch-repair deficient (29/127, 23%) and polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression analysis shows strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker. Tertiary lymphoid structures (TLS) are associated with a reduced risk of cancer recurrence and improved response to immune checkpoint blockade in several tumor types. Here the authors identify L1CAM as a marker for mature TLS and show that the presence of TLS is associated with favorable prognosis in patients with endometrial cancer from the PORTEC-3 trial.

引用

页数：10

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