GIGA 2021 Annual Report 45 SELECTED PUBLICATIONS Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence. Luis G, Godfroid A, Nishiumi S, Cimino J, Blacher S, Maquoi E, Wery C, Collignon A, Longuespée R, Montero-Ruiz L, Dassoul I, Maloujahmoum N, Pottier C, Mazzucchelli G, Depauw E, Bellahcène A, Yoshida M, Noel A, Sounni NE. Redox Biol. 2021 Jul;43:102006. Activation of DNA damage tolerance pathways may improve immunotherapy of mesothelioma. Hélène Brossel, Alexis Fontaine, Clotilde Hoyos, Majeed Jamakhani, Mégane Willems, Malik Hamaidia and Luc Willems. Cancers 2021 13:3211 Tumor exposed-lymphatic endothelial cells promote primary tumor growth via IL6. Van de Velde M, Ebroin M, Durré T, Joiret M, Gillot L, Blacher S, Geris L, Kridelka F, Noel A. Cancer Lett. 2021 497:154-164. Treatment algorithm and prognostic factors for patients with stage I-III carcinoma of the anal canal: a 20-year multicenter study. Bruyere D, Monnien F, Colpart P, Roncarati P, Vuitton L, Hendrick E, Lepinoy A, Luquain A, Pilard C, Lerho T, Molimard C, Maingon P, Arnould L, Bone-Lepinoy MC, Dusserre L, Martin L, Reynders C, Ancion M, Peiffert D, Leroux A, Hubert P, Delhorme JB, Ghnassia JP, Woronoff AS, Delvenne P, Prétet JL, Bosset JF, Peulen O, Mougin C, Valmary-Degano S, & Herfs M. Mod Pathol. 2021; 34(1):116-130. Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy. Hubert P, Roncarati P, Demoulin S, Pilard C, Ancion M, Reynders C, Lerho T, Bruyere D, Lebeau A, Radermecker C, Meunier M, Nokin MJ, Hendrick E, Peulen O, Delvenne P, & Herfs M. J Immunother Cancer. 2021; 9(3):e001966. SARS-CoV-2 in carotid body. Lambermont B, Davenne E, Maclot F, Delvenne P. Intensive Care Medicine 47 (2021), 342-343. FUNCTIONS OF LYMPHATIC ENDOTHELIAL CELLS EXPOSED TO TUMOR CELLS: BEYOND THE FORMATION OF LYMPHATIC VESSELS. Solid tumors are composed of tumor cells and stromal cells including lymphatic endothelial cells (LECs). LECs are mainly viewed as passive cells forming lymphatic vessels involved in the transport of metastatic cells and immune cells. We here provide evidence for novel pro- tumorigenic functions of tumor exposed-LECs (teLECs) in the tumor environment. The characterization of teLEC secretome by RNA- Sequencing and cytokine arrays revealed that interleukine-6 (IL6) is one of the most modulated molecules in teLECs, whose production was negligible in normal LECs. IL6-derived teLEC exerts mitogenic effect on tumor cells, in the primary tumor and this was completely abrogated in vivo by neutralizing anti-human IL6 antibody. This work highlights a new paradigm, in which teLECs act as “fibroblast-like cells” in the tumor microenvironment and contribute, in a paracrine manner, to the control of tumor cell properties. This work warrants to revisit the “vascular-centric view” of LECs and demonstrate that LECS are worth considering as key stromal determinant of the tumor microenvironment in future studies. Tumor exposed-lymphatic endothelial cells promote primary tumor growth via IL6. Van de Velde M, Ebroin M, Durré T, Joiret M, Gillot L, Blacher S, Geris L, Kridelka F, Noel A. Cancer Lett. 2021 497:154-164.
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