A Proteomic Atlas of Lineage and Cancer-Polarized Expression Modules in Myeloid Cells Modeling Immunosuppressive Tumor-Infiltrating Subsets

被引：5

作者：

Blanco, Ester ^{[1
]}

Ibanez-Vea, Maria ^{[1
,2
]}

Hernandez, Carlos ^{[1
]}

Drici, Lylia ^{[3
]}

Martinez de Morentin, Xabier ^{[4
]}

Gato, Maria ^{[1
]}

Ausin, Karina ^{[5
]}

Bocanegra, Ana ^{[1
]}

Zuazo, Miren ^{[1
]}

Chocarro, Luisa ^{[1
]}

Arasanz, Hugo ^{[1
]}

Fernandez-Hinojal, Gonzalo ^{[1
]}

Fernandez-Irigoyen, Joaquin ^{[5
]}

Smerdou, Cristian ^{[6
,7
]}

Garnica, Maider ^{[1
]}

Echaide, Miriam ^{[1
]}

Fernandez, Leticia ^{[1
]}

Morente, Pilar ^{[1
]}

Ramos-Castellanos, Pablo ^{[1
]}

Llopiz, Diana ^{[8
,9
,10
]}

Santamaria, Enrique ^{[5
]}

Larsen, Martin R. ^{[11
]}

Escors, David ^{[1
]}

Kochan, Grazyna ^{[1
]}

机构：

[1] Fdn Miguel Servet Complejo Hospitalario Navarra U, Oncoimmunol Grp, Navarrabiomed, Pamplona 31008, Spain

[2] Univ Publ Navarra, Inst Multidisciplinary Res Appl Biol IMAB UPNA, Genet Genom & Microbiol Res Grp, Campus Arrosadia, Pamplona 31006, Spain

[3] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Prot Res, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark

[4] Navarra Inst Hlth Res IdiSNA, Inst Hlth Carlos III ISCIII, Bioinformat Grp, Navarrabiomed Biomed Res Ctr, Irunlarrea 3, Pamplona 31008, Spain

[5] Univ Publ Navarra UPNA, Complejo Hospitalario Navarra CHN, Proteored ISCIII, Prote Platform,Navarrabiomed,IdISNA, Irunlarrea 3, Pamplona 31008, Spain

[6] Cima Univ Navarra, Div Gene Therapy & Regulat Gene Express, Pamplona 31008, Spain

[7] Inst Invest Sanitaria Navarra IdISNA, Pamplona 31008, Spain

[8] Univ Navarra, Ctr Invest Med Aplicada CIMA, Pamplona 31008, Spain

[9] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Pamplona 31008, Spain

[10] Inst Invest Sanitaria Navarra, IdiSNA, Pamplona 31008, Spain

[11] Univ Southern Denmark, Dept Biochem & Mol Biol, Campusvej 55, DK-5230 Odense M, Denmark

来源：

JOURNAL OF PERSONALIZED MEDICINE | 2021年 / 11卷 / 06期

基金：

欧盟地平线“2020”;

关键词：

myeloid-derived suppressor cells; cancer; tumor-infiltrating macrophages; SUPPRESSOR-CELLS; DIFFERENTIATION; MACROPHAGES; ACCUMULATION; CATHEPSINS; ACTIVATION; PROTEINS; TARGETS; MOUSE;

D O I：

10.3390/jpm11060542

中图分类号：

R19 [保健组织与事业（卫生事业管理）];

学科分类号：

摘要：

Monocytic and granulocytic myeloid-derived suppressor cells together with tumor-infiltrating macrophages constitute the main tumor-infiltrating immunosuppressive myeloid populations. Due to the phenotypic resemblance to conventional myeloid cells, their identification and purification from within the tumors is technically difficult and makes their study a challenge. We differentiated myeloid cells modeling the three main tumor-infiltrating types together with uncommitted macrophages, using ex vivo differentiation methods resembling the tumor microenvironment. The phenotype and proteome of these cells was compared to identify linage-dependent relationships and cancer-specific interactome expression modules. The relationships between monocytic MDSCs and TAMs, monocytic MDSCs and granulocytic MDSCs, and hierarchical relationships of expression networks and transcription factors due to lineage and cancer polarization were mapped. Highly purified immunosuppressive myeloid cell populations that model tumor-infiltrating counterparts were systematically analyzed by quantitative proteomics. Full functional interactome maps have been generated to characterize at high resolution the relationships between the three main myeloid tumor-infiltrating cell types. Our data highlights the biological processes related to each cell type, and uncover novel shared and differential molecular targets. Moreover, the high numbers and fidelity of ex vivo-generated subsets to their natural tumor-shaped counterparts enable their use for validation of new treatments in high-throughput experiments.

引用

页数：21