Inflammation, Complement and Cancer

Director : 

Isabelle Cremer

Deputy Director : 

Lubka Roumenina

 

In the Inflammation, Complement and Cancer team, our missions are:

1) To decipher the molecular and cellular mechanisms of the complex interplay between the tumor and its immune microenvironment and how these interactions are modulated by external microbial stimuli or by immunotherapy.

2) To understand how complement overactivation contributes to the

pathogenesis of renal diseases.

Scientific Themes

Inflammation and cancer

The lung tumor immune environment is highly heterogeneous and inflammatory. The origin of such heterogeneity is not fully understood and could be driven by carcinogen exposure, microbial infections including Respiratory Syncytial, Influenza and Coronaviruses), host immune system or tumor cells characteristics (genetics, epigenetics, metabolism). Our goal is to understand physiologic, cellular and molecular mechanisms leading to such heterogeneity, which influences the clinical outcome of tumor bearing patients, and the responses to anti-tumor treatments.

Immunotherapy and cancer

The goal of the cancer immunotherapy team is to find predictive biomarkers of response to immune check point blockade and to decipher mechanisms of resistance to immunotherapy in the tumor microenvironment, using large retrospective cohorts of patients with cancers and prospective trials in national and international cooperative investigations.

Complement in physiology and pathology

We study the role of the innate immune complement system as driver of tissue injury. We are interested by the functioning of complement in physiology and in its disbalance a large spectrum of pathologies, including typical complement-mediated diseases but also diseases for which we bring complement to the pathophysiological picture. We carry out basic science and translational research.

Main publications

INFLAMMATION AND CANCER

  • Damotte D, Warren S, Arrondeau J, Boudou-Rouquette P, Mansuet-Lupo A, Biton J, Ouakrim H, Alifano M, Gervais C, Bellesoeur A, Kramkimel N, Tlemsani C, Burroni B, Duche A, Letourneur F, Si H, Halpin R, Creasy T, Herbst R, Ren X, Morel P, Cesano A, Goldwasser F, Leroy K. The tumor inflammation signature (TIS) is associated with anti-PD-1 treatment benefit in the CERTIM pan-cancer cohort. J Transl Med. 2019 Nov 4;17(1):357. doi: 10.1186/s12967-019-2100-3.PMID: 31684954
  • Mansuet-Lupo A, Barritault M,Alifano M, Janet-Vendroux A, Zarmaev M, Biton J, Velut Y, Le Hay C, Cremer I, Régnard JF, Fournel L, Rance B, Wislez M, Laurent-Puig P, Herbst R, Damotte D, Blons H. Proposal for a Combined Histomolecular Algorithm to Distinguish Multiple Primary Adenocarcinomas from Intrapulmonary Metastasis in Patients with Multiple Lung Tumors. J Thorac Oncol. 2019 May;14(5):844-856. doi: 10.1016/j.jtho.2019.01.017. Epub 2019 Feb 2.PMID: 30721797
  • Dajon M, Iribarren K, Petitprez F, Marmier S, Lupo A, Gillard M, Ouakrim H, Victor N, Vincenzo DB, Joubert PE, Kepp O, Kroemer G,Alifano M, Damotte D, Cremer I. Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells. 2018 Oct 11;8(1):e1505174. doi: 10.1080/2162402X.2018.1505174. PMID: 30546943
  • Milcent B, Josseaume N, Riller Q, Giglioli I, Rabia E, Deligne C, Latouche JB, Hamieh M, Couture A, Toutirais O, Lone YC, Jeger-Madiot R, Graff-Dubois S, Amorim S, Loiseau P, Toubert A, Brice P, Thieblemont C, Teillaud JL,Sibéril S. Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients. Cancer Immunol Immunother. 2019 Oct;68(10):1561-1572. doi: 10.1007/s00262-019-02389-7. PMID: 31494742
  • Biton J, Mansuet-Lupo A, Pécuchet N, Alifano M, Ouakrim H, Arrondeau J, Boudou-Rouquette P, Goldwasser F, Leroy K, Goc J, Wislez M, Germain C, Laurent-Puig P, Dieu-Nosjean MC,Cremer I, Herbst R, Blons H, Damotte D. TP53, STK11, and EGFR Mutations Predict Tumor Immune Profile and the Response to Anti-PD-1 in Lung Adenocarcinoma. Clin Cancer Res. 2018 Nov 15;24(22):5710-5723. doi: 10.1158/1078-0432.CCR-18-0163. Epub 2018 May 15.PMID: 29764856

IMMUNOTHERAPY AND CANCER

  • Petitprez, A. de Reyniès, E. Z. Keung, T.W. Chen, C.M. Sun, J. Calderaro, Y.M. Jeng, L.P. Hsiao, L. Lacroix, A. Bougoüin, M. Moreira, G. Lacroix, I. Natario, J. Adam, C. Lucchesi, Y. Laizet M. Toulmonde, A. Burgess, V. Bolejack, D. Reinke, K. M. Wani, W.L. Wang, A. J. Lazar, C. L. Roland, J. A. Wargo, A. Italiano, C. Sautès-Fridman, H. A. Tawbi and W.H. Fridman. B cells are associated with sarcoma survival and immunotherapy response, Nature, 2020 577:556-560. (with News and views)
  • Sautès-Fridman C, Petitprez F, Calderaro F, Fridman WH. Tertiary Lymphoid Structures in the era of cancer therapy. Nature Reviews Cancer, 2019,19:307-325.
  • Calderaro J, Petitprez F, Becht E, Laurent A, Hirsch TZ, Rousseau B, Luciani A, Amaddeo G, Derman J, Charpy C, Zucman-Rossi J, Fridman WH, Sautès-Fridman C. Intra-tumoral tertiary lymphoid structures are associated with a low risk of early recurrence of hepatocellular carcinoma. J Hepatol. 2019 70:58-65.
  • Fridman WH, Zitvogel L, Sautès-Fridman C, Kroemer G. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol. 2017 14:717-734.
  • Becht E, de Reyniès A, Giraldo NA, Pilati C, Buttard B, Lacroix L, Sèlves J, Sautès-Fridman C, Laurent-Puig P, Fridman WH. (2016) Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy. Clin Cancer Res. pii: clincanres.2879.

 

COMPLEMENT IN PHYSIOLOGY AND PATHOLOGY

  • Chauvet S, Berthaud R, Devriese M, Mignotet M, Vieira Martins P, Robe-Rybkine T, Miteva MA, Gyulkhandanyan A, Ryckewaert A, Louillet F, Merieau E, Mestrallet G, Rousset-Rouvière C, Thervet E, Hogan J, Ulinski T, Villoutreix BO, Roumenina L, Boyer O, Frémeaux-Bacchi V. Anti-Factor B Antibodies and Acute Postinfectious GN in Children. J Am Soc Nephrol. 2020; 31(4):829-840.
  • Merle NS, Paule R, Leon J, Daugan M, Robe-Rybkine T, Poillerat V, Torset C, Frémeaux-Bacchi V, Dimitrov JD, Roumenina LT. P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4/heme-dependent manner.; Proc Natl Acad Sci U S A. 2019; 26;116(13):6280-6285
  • Roumenina LT, Daugan MV, Petitprez F, Sautès-Fridman C, Fridman WH. Context-dependent roles of complement in cancer., Nat Rev Cancer. 2019;19(12):698-715.
  • Marinozzi MC, Chauvet S, Le Quintrec M, Mignotet M, Petitprez F, Legendre C, Cailliez M, Deschenes G, Fischbach M, Karras A, Nobili F, Pietrement C, Dragon-Durey MA, Fakhouri F, Roumenina LT, Fremeaux-Bacchi V., C5 nephritic factors drive the biological phenotype of C3 glomerulopathies., Kidney Int. 2017; 92(5):1232-1241.
  • Togarsimalemath SK, Sethi SK, Duggal R, Le Quintrec M, Jha P, Daniel R, Gonnet F, Bansal S, Roumenina LT, Fremeaux-Bacchi V, Kher V, Dragon-Durey MA., A novel CFHR1-CFHR5 hybrid leads to a familial dominant C3 glomerulopathy., Kidney Int. 2017; 92(4):876-887.

All publications

Fundings