Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion

被引：48

作者：

Zeng, Qiqun ^{[1
,2
]}

Saghafinia, Sadegh ^{[1
,2
]}

Chryplewicz, Agnieszka ^{[1
,3
]}

Fournier, Nadine ^{[4
]}

Christe, Lucine ^{[5
]}

Xie, Yu-Qing ^{[6
]}

Guillot, Jeremy ^{[1
,3
]}

Yucel, Simge ^{[1
,3
]}

Li, Pumin ^{[1
,3
,7
]}

Galvan, Jose A. ^{[5
]}

Karamitopoulou, Eva ^{[5
]}

Zlobec, Inti ^{[5
]}

Ataca, Dalya ^{[2
]}

Gallean, Fleuriane ^{[2
]}

Zhang, Peng ^{[8
]}

Rodriguez-Calero, Jose Antonio ^{[9
]}

Rubin, Mark ^{[9
]}

Tichet, Melanie ^{[1
,3
,10
]}

Homicsko, Krisztian ^{[1
,3
,10
,11
,12
]}

Hanahan, Douglas ^{[1
,3
,10
,12
]}

机构：

[1] Swiss Fed Inst Technol Lausanne EPFL, Swiss Inst Expt Canc Res ISREC, Sch Life Sci, CH-1015 Lausanne, Switzerland

[2] Opna Bio SA, Biopole, CH-1066 Epalinges, Switzerland

[3] Agora Canc Res Ctr, CH-1011 Lausanne, Switzerland

[4] Swiss Inst Bioinformat SIB, CH-1015 Lausanne, Switzerland

[5] Univ Bern, Inst Pathol, CH-3008 Bern, Switzerland

[6] Swiss Fed Inst Technol Lausanne EPFL, Inst Bioengn, Sch Engn, CH-1015 Lausanne, Switzerland

[7] Univ Lausanne, Dept Computat Biol, CH-1015 Lausanne, Switzerland

[8] Capital Med Univ, Beijing Pediat Res Inst, Beijing Childrens Hosp, Natl Ctr Childrens Hlth, Beijing 100045, Peoples R China

[9] Univ Bern, Dept BioMed Res, CH-3008 Bern, Switzerland

[10] Ludwig Inst Canc Res, Lausanne Branch, CH-1011 Lausanne, Switzerland

[11] Univ Hosp Lausanne CHUV, Dept Oncol, CH-1011 Lausanne, Switzerland

[12] Swiss Canc Ctr Leman SCCL, CH-1011 Lausanne, Switzerland

来源：

SCIENCE | 2022年 / 378卷 / 6621期

基金：

瑞士国家科学基金会;

关键词：

D O I：

10.1126/science.abl7207

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：

Many human cancers manifest the capability to circumvent attack by the adaptive immune system. In this work, we identified a component of immune evasion that involves frequent up-regulation of fragile X mental retardation protein (FMRP) in solid tumors. FMRP represses immune attack, as revealed by cancer cells engineered to lack its expression. FMRP-deficient tumors were infiltrated by activated T cells that impaired tumor growth and enhanced survival in mice. Mechanistically, FMRP's immunosuppression was multifactorial, involving repression of the chemoattractant C-C motif chemokine ligand 7 (CCL7) concomitant with up-regulation of three immunomodulators-interleukin-33 (IL-33), tumor-secreted protein S (PROS1), and extracellular vesicles. Gene signatures associate FMRP's cancer network with poor prognosis and response to therapy in cancer patients. Collectively, FMRP is implicated as a regulator that orchestrates a multifaceted barrier to antitumor immune responses.

引用

页数：24

共 85 条

[1] scGate: marker-based purification of cell types from heterogeneous single-cell RNA-seq datasets [J].

Andreatta, Massimo ;

Berenstein, Ariel J. ;

Carmona, Santiago J. .

BIOINFORMATICS, 2022, 38 (09) :2642-2644

[2] Interpretation of T cell states from single-cell transcriptomics data using reference atlases [J].

Andreatta, Massimo ;

Corria-Osorio, Jesus ;

Muller, Soren ;

Cubas, Rafael ;

Coukos, George ;

Carmona, Santiago J. .

NATURE COMMUNICATIONS, 2021, 12 (01)

[3]

BAKKER CE, 1994, CELL, V78, P23

[4] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[5]

Bayraktar Soley, 2019, J Carcinog, V18, P2, DOI 10.4103/jcar.JCar_2_19

[6] Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].

Brahmer, Julie R. ;

Tykodi, Scott S. ;

Chow, Laura Q. M. ;

Hwu, Wen-Jen ;

Topalian, Suzanne L. ;

Hwu, Patrick ;

Drake, Charles G. ;

Camacho, Luis H. ;

Kauh, John ;

Odunsi, Kunle ;

Pitot, Henry C. ;

Hamid, Omid ;

Bhatia, Shailender ;

Martins, Renato ;

Eaton, Keith ;

Chen, Shuming ;

Salay, Theresa M. ;

Alaparthy, Suresh ;

Grosso, Joseph F. ;

Korman, Alan J. ;

Parker, Susan M. ;

Agrawal, Shruti ;

Goldberg, Stacie M. ;

Pardoll, Drew M. ;

Gupta, Ashok ;

Wigginton, Jon M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465

[7] Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma [J].

Castle, John C. ;

Loewer, Martin ;

Boegel, Sebastian ;

de Graaf, Jos ;

Bender, Christian ;

Tadmor, Arbel D. ;

Boisguerin, Valesca ;

Bukur, Thomas ;

Sorn, Patrick ;

Paret, Claudia ;

Diken, Mustafa ;

Kreiter, Sebastian ;

Tureci, Ozlem ;

Sahin, Ugur .

BMC GENOMICS, 2014, 15

[8] Exosome-Mediated Crosstalk Between Tumor and Tumor-Associated Macrophages [J].

Chen, Qi ;

Li, Yuefeng ;

Gao, Wujiang ;

Chen, Lu ;

Xu, Wenlin ;

Zhu, Xiaolan .

FRONTIERS IN MOLECULAR BIOSCIENCES, 2021, 8

[9] A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells [J].

Cheng, Sijin ;

Li, Ziyi ;

Gao, Ranran ;

Xing, Baocai ;

Gao, Yunong ;

Yang, Yu ;

Qin, Shishang ;

Zhang, Lei ;

Ouyang, Hanqiang ;

Du, Peng ;

Jiang, Liang ;

Zhang, Bin ;

Yang, Yue ;

Wang, Xiliang ;

Ren, Xianwen ;

Bei, Jin-Xin ;

Hu, Xueda ;

Bu, Zhaode ;

Ji, Jiafu ;

Zhang, Zemin .

CELL, 2021, 184 (03) :792-+

[10] Intratumoral Activity of the CXCR3 Chemokine System Is Required for the Efficacy of Anti-PD-1 Therapy [J].

Chow, Melvyn T. ;

Ozga, Aleksandra J. ;

Servis, Rachel L. ;

Frederick, Dennie T. ;

Lo, Jennifer A. ;

Fisher, David E. ;

Freeman, Gordon J. ;

Boland, Genevieve M. ;

Luster, Andrew D. .

IMMUNITY, 2019, 50 (06) :1498-+

← 1 2 3 4 5 6 7 8 9 →