Inflammation, Complement and Cancer

Director : 

Isabelle Cremer

Deputy Director : 

Lubka Roumenina


The mission of the InC2 team is to provide better understanding of the structural and functional organization of the tissue immune microenvironment with a particular focus on cancer (lung, renal, sarcoma, lymphoma) and renal diseases. By integrating functional exploration, multi-omics approaches (spatial transcriptomics, scRNAseq, ultra-highly multiplexed imaging…) and computational analysis, we aim to:

  • Characterize at molecular and cellular level the mechanisms implicating the immune system in the disease evolution control and response to treatment.
  • Identify novel therapeutic targets and biomarkers to follow prognosis and response to treatment.
  • Improve patients’ management, finding the most adapted therapy to each patient, allowing increased treatment efficacy, reduced adverse effects and cost of treatments.

Scientific Themes

Inflammation and cancer

The goals of the Inflammation and Cancer group are to characterize the host cellular and molecular events that shape the tumor microenvironment and how this influences response to anti-tumor treatments, and to determine how viral infections reprogram the tumor microenvironment.

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.

Complement in physiology and pathology

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

Main publications

Group inflammation, complement and cancer

Acute Influenza Infection Promotes Lung Tumor Growth by Reprogramming the Tumor Microenvironment. Garmendia I, Varthaman A, Marmier S, Angrini M, Matchoua I, Darbois-Delahousse A, Josseaume N, Foy PE, Roumenina LT, Naouar N, Meylan M, Sibéril S, Russick J, Joubert PE, Leroy K, Damotte D, Mansuet-Lupo A, Wislez M, Alifano M, Menger L, Garcia-Verdugo I, Sallenave JM, Lantz O, Petitprez F, Cremer I. Cancer Immunol Res. 2023 Apr 3;11(4):530-545. doi: 10.1158/2326-6066.CIR-22-0534.PMID: 36883368 link


SMARCA4-deficient lung carcinoma is an aggressive tumor highly infiltrated by FOXP3+ cells and neutrophils. Velut Y, Decroix E, Blons H, Alifano M, Leroy K, Petitprez F, Boni A, Garinet S, Biton J, Cremer I, Wislez M, Boudou-Rouquette P, Arrondeau J, Goldwasser F, Fournel L, Damotte D, Mansuet-Lupo A. Lung Cancer. 2022 Jul;169:13-21. doi: 10.1016/j.lungcan.2022.05.001. Epub 2022 May 5.PMID: 35597058 link


Autophagy-Related Gene Signature Highlights Metabolic and Immunogenic Status of Malignant Cells in Non-Small Cell Lung Cancer Adenocarcinoma. Leonardi L, Siberil S, Alifano M, Cremer I, Joubert PE.Cancers (Basel). 2022 Jul 16;14(14):3462. doi: 10.3390/cancers14143462.PMID: 35884522 link


Immune Signature Linked to COVID-19 Severity: A SARS-Score for Personalized Medicine. Russick J, Foy PE, Josseaume N, Meylan M, Hamouda NB, Kirilovsky A, Sissy CE, Tartour E, Smadja DM, Karras A, Hulot JS, Livrozet M, Fayol A, Arlet JB, Diehl JL, Dragon-Durey MA, Pagès F, Cremer I. Front Immunol. 2021 Jul 12;12:701273. doi: 10.3389/fimmu.2021.701273. eCollection 2021.PMID: 34322128 link


Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions. Russick J, Joubert PE, Gillard-Bocquet M, Torset C, Meylan M, Petitprez F, Dragon-Durey MA, Marmier S, Varthaman A, Josseaume N, Germain C, Goc J, Dieu-Nosjean MC, Validire P, Fournel L, Zitvogel L, Bindea G, Lupo A, Damotte D, Alifano M, Cremer I. J Immunother Cancer. 2020 Oct;8(2):e001054. doi: 10.1136/jitc-2020-001054.PMID: 33067317 link


Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non-small-cell lung carcinoma. Boulle G, Velut Y, Mansuet-Lupo A, Gibault L, Blons H, Fournel L, Boni A, Cremer I, Wislez M, Duchatelle V, Trédaniel J, Hammond SA, Herbst R, Alifano M, Giraud P, Damotte D. Eur J Cancer. 2020 Aug;135:221-229. doi: 10.1016/j.ejca.2020.04.040. Epub 2020 Jun 28.PMID: 32610210 link


Group Immunotherapy and cancer

Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer. Meylan M, Petitprez F, Becht E, Bougouin A, Pupier G, Calvez A, Giglioli I, Verkarre V, Lacroix G, Verneau J, Sun CM, Laurent-Puig P, Vano YA, Elaïdi R, Méjean A, Sanchez-Salas R, Barret E, Cathelineau X, Oudard S, Reynaud CA, de Reyniès A, Sautès-Fridman C, Fridman WH. Immunity. 2022 Mar 8;55(3):527-541.e5. doi: 10.1016/j.immuni.2022.02.001. Epub 2022 Feb 28.PMID: 35231421 link


Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort. Italiano A, Bessede A, Pulido M, Bompas E, Piperno-Neumann S, Chevreau C, Penel N, Bertucci F, Toulmonde M, Bellera C, Guegan JP, Rey C, Sautès-Fridman C, Bougouin A, Cantarel C, Kind M, Spalato M, Dadone-Montaudie B, Le Loarer F, Blay JY, Fridman WH. Nat Med. 2022 Jun;28(6):1199-1206. link


B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome. Fridman WH, Meylan M, Petitprez F, Sun CM, Italiano A, Sautès-Fridman C. Nat Rev Clin Oncol. 2022 Jul;19(7):441-457. Review. link


Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression. Vanhersecke L, Brunet M, Guégan JP, Rey C, Bougouin A, Cousin S, Moulec SL, Besse B, Loriot Y, Larroquette M, Soubeyran I, Toulmonde M, Roubaud G, Pernot S, Cabart M, Chomy F, Lefevre C, Bourcier K, Kind M, Giglioli I, Sautès-Fridman C, Velasco V, Courgeon F, Oflazoglu E, Savina A, Marabelle A, Soria JC, Bellera C, Sofeu C, Bessede A, Fridman WH, Loarer FL, Italiano A. Nat Cancer. 2021 Aug;2(8):794-802. doi: 10.1038/s43018-021-00232-6. Epub 2021 Aug 12.PMID: 35118423 link


B cells are associated with survival and immunotherapy response in sarcoma. Petitprez F, de Reyniès A, Keung EZ, Chen TW, Sun CM, Calderaro J, Jeng YM, Hsiao LP, Lacroix L, Bougoüin A, Moreira M, Lacroix G, Natario I, Adam J, Lucchesi C, Laizet YH, Toulmonde M, Burgess MA, Bolejack V, Reinke D, Wani KM, Wang WL, Lazar AJ, Roland CL, Wargo JA, Italiano A, Sautès-Fridman C, Tawbi HA, Fridman WH. Nature. 2020 Jan;577(7791):556-560. doi: 10.1038/s41586-019-1906-8. Epub 2020 Jan 15.PMID: 31942077 link


Group Complement in physiology and pathology

C1q+ macrophages: passengers or drivers of cancer progression.  Revel M, Sautès-Fridman C, Fridman WH, Roumenina LT. Trends Cancer. 2022 Mar 11:S2405-8033(22)00042-5. doi: 10.1016/j.trecan.2022.02.006. PMID: 35288093 Review. link

Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s.  Daugan MV, Revel M, Russick J, Dragon-Durey MA, Gaboriaud C, Robe-Rybkine T, Poillerat V, Grunenwald A, Lacroix G, Bougouin A, Meylan M, Verkarre V, Oudard SM, Mejean A, Vano YA, Perkins G, Validire P, Cathelineau X, Sanchez-Salas R, Damotte D, Fremeaux-Bacchi V, Cremer I, Sautès-Fridman C, Fridman WH, Roumenina LT. Cancer Immunol Res. 2021 Aug;9(8):891-908. doi: 10.1158/2326-6066.CIR-20-0532. PMID: 34039653 link

Intracellular Factor H Drives Tumor Progression Independently of the Complement Cascade.  Daugan MV, Revel M, Thouenon R, Dragon-Durey MA, Robe-Rybkine T, Torset C, Merle NS, Noé R, Verkarre V, Oudard SM, Mejean A, Validire P, Cathelineau X, Sanchez-Salas R, Pickering MC, Cremer I, Mansuet-Lupo A, Alifano M, Sautès-Fridman C, Damotte D, Fridman WH, Roumenina LT. Cancer Immunol Res. 2021 Aug;9(8):909-925. doi: 10.1158/2326-6066.CIR-20-0787. PMID: 34039652 link

Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis.  Boudhabhay I, Poillerat V, Grunenwald A, Torset C, Leon J, Daugan MV, Lucibello F, El Karoui K, Ydee A, Chauvet S, Girardie P, Sacks S, Farrar CA, Garred P, Berthaud R, Le Quintrec M, Rabant M, de Lonlay P, Rambaud C, Gnemmi V, Fremeaux-Bacchi V, Frimat M, Roumenina LT. Kidney Int. 2021 Mar;99(3):581-597. doi: 10.1016/j.kint.2020.09.033. PMID: 33137339 link

Anti-Factor B Antibodies and Acute Postinfectious GN in Children.  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. J Am Soc Nephrol. 2020 Apr;31(4):829-840. doi: 10.1681/ASN.2019080851. PMID: 32034108 link

All publications