AccueilAccueil>La recherche>Teams>Jérôme GALON

Integrative Cancer Immunology

We hypothesize that integrative biology approaches will provide a better knowledge of the local interplay between the immune components and the tumor cells. In particular, the research project is focusing on the analysis of the tumor microenvironment, and of immune response against cancer with basic and clinical aspects.

The objectives of this project are to develop innovations in oncology research, based on a better global understanding of the tumor microenvironment and of the dynamics of the host-immune response in human, using high-throughput methods, novel technologies, and integrative biology approaches.

The laboratory is open to collaborators from very diverse disciplines such as immunology, oncology, math, computer science, bioinformatics, statistics, biostatistics, chemistry, physics, genetics, microbiology, … They are welcome to join the team to tackle ambitious questions including :

Is the immune system important against cancer, and which immune reaction would be required?

How to understand the host immune response against cancer during tumor evolution?

Is there a correlative or rather a causative relationship between intratumoral immune reaction and tumor development?

Why is the presence of a memory T cell reaction within the primary tumor, prognostic? Why is the primary tumor not eliminated by the immune system?

Which immune events and/or tumor events lead to inadequate host-immune response in the control of tumor development? and of tumor relapse?

What are the immune escape mechanisms in human cancer?

How to identify patients with poor prognosis who would benefit from adjuvant therapy?

How to classify cancer patients based on immune characteristics?

How to develop an efficient cancer immunotherapy?

We have developed a multi-disciplinary network with research scientists in immunology and oncology, clinical teams and bioinformaticians. Global understanding of cancer requires the integration and analysis of genomic, proteomic, transcriptomic, molecular, cellular, as well as clinical data and requires bioinformatics. Bioinformatics nowadays has an essential role both, in deciphering data generated by high-throughput experimental technologies, and in organizing information gathered from traditional biology and medicine.

Bioinformaticians from the laboratory built specific databases for (i) clinical and biological data, (ii) experimental data like DNA microarrays, aCGH, tissue microarray, sequencing data, FACS and (iii) Software for data integration, analysis and visualization, such as ClueGO and CluePedia.


The Laboratory Integrative Cancer Immunology is part of the Cordeliers Research Center from Paris. Our team has also a translational laboratory at the immunomonitoring platform of the European Hospital George Pompidou.

Major Discoveries:
Immune contexture in cancer:

Using systems biology, the laboratory developed a comprehensive analysis of the in situ immune reaction at tumor site of colorectal cancers, and we discovered the major importance the nature, the functional orientation, the density and the localization of immune cell populations within the tumor. We defined these 4 parameters as the immune contexture. Our data reveals that the immune contexture at tumor site determines cancer evolution and clinical outcome regardless of the local extent and spread of the tumor. Using systems biology, we characterized the immune landscape in human cancer.
We showed that a high density of memory T lymphocytes (CD45RO) correlated with the absence of early-metastatic invasion (VELIPI). Analyses reveal the strength of the in situ immune contexture on clinical outcome at all stages of the disease, including patients with early stage cancer. This had never been shown in any human tumor. This un-described strength of the immune reaction changes the understanding of cancer's evolution and could have important consequences in clinical practice.

Major references :
(N Engl J Med, 2005 ; Science, 2006 ; Cancer Res 2007 ; Gastroenterology 2009 ; Bioinformatics 2009 ; Cancer Res 2009 ; Cancer Res 2011 ; Curr Op Immunol 2010 ; Curr Op Immunol 2011 ; Nature Rev Cancer 2012, Curr Op Immunol 2013, Immunity 2013a, Immunity 2013b, 2018; Science Transl Med 2014, JNCI, 2018; Cell 2018).

Immunoscore:

We discovered that the characterization of the adaptive immune reaction that was a better predictor of survival than traditional staging based on a cancer's size and spread. In particular this should lead to recast the currently used classification of colorectal cancers (only based on tumor criteria) for predicting clinical outcome, and refine the patient groups that are at high-risk of tumor recurrence who may benefit from adjuvant therapy (including immunotherapy). This immune-classification has a prognostic value that is superior to the AJCC/UICC TNM-classification, and tumor invasion was shown to be, in fact, statistically dependent on the host-immune reaction. Indeed, the immune pattern remained the only significant criterion over the classical AJCC/UICC TNM classification for disease free and overall survival, and led to an editorial entitled “TNM staging in colorectal cancer: T is for T cell and M is for memory” accompanying our publication. Our studies show the potential usefulness to extend this concept and these techniques to the investigation of all malignant tumors. Information about the Immunoscore can be found at http://www.immunoscore.org

The strong prognostic value of the Immunoscore® assay in early stage colon cancer was confirmed by an international consortium led by the Society for Immunotherapy of Cancer (SITC), and conducted in 14 expert centers worldwide (Pages et al, The Lancet, 2018). These results validate the reliability of Immunoscore® Colon in identifying patients with a high risk of recurrence, independently of the TNM staging system.
Major references :
(Inserm Patent 2005, 2010, 2011, 2012 ; N Engl J Med, 2005 ; Science, 2006 ; J Clin Oncol 2009 ; J Clin Oncol 2011 ; J Transl Med 2012 ; J pathol 2014, The Lancet, 2018).


HalioDx – Immuno-Oncology Diagnostic company
Co-founder Dr. Jérôme Galon
www.haliodx.com

HalioDx vision is to create a leader in Immuno-Oncology diagnostics, the emerging segment of the cancer molecular diagnostic market (MDx). Dr. Jérôme Galon is a co-founder of HalioDx. The co-founders are experienced executives with extensive track records in the Diagnostic Industry (Ipsogen, Qiagen), Pharma & BioTech Management.


Bioinformatics
We have developed novel software tools, including ClueGO and CluPedia, Cytoscape Apps (Bindea G, et al. Bioinformatics. 2009, 2013, Mlecnik et al. JProteomics 2018) that are broadly used by the scientific community. More information about these software can be found at: http://www.ici.upmc.fr and http://apps.cytoscape.org/



Team Leader:  Jérome GALON (DR; Inserm)

 

Team Members :
Researchers: Anne BERGER (PUPH; Univ Paris Descartes), Gabriela BINDEA (CR; Inserm), Christine LAGORCE (MD, AP-HP), Bernhard MLECNIK (CR; Innovarion), Franck PAGES (PU-PH; Paris Descartes), Guy ZEITOUN (PH; AP-HP).

Technical Staff: Myriam ESKANDAR (IE; Inserm), Tessa FREDRIKSEN (AI; Sorbonne Univ), Lucie LAFONTAINE (Tec; Sorbonne Univ), Florence MARLIOT (IE; Paris Descartes).

Young Researchers: Mihaela ANGELOVA (Post-Doc; Inserm), Bénédicte BUTTARD (PhD Student; Inserm),  Carine EL SISSY (Doct; AP-HP), Amos KIRILOVSKI (Post-Doc; Inserm), Erwan MORGAN (PhD Student; Inserm),  Daniela BRUNI (Post-Doc; Inserm).

Administration: Mehdi BENNACI (Adj Tec; Paris Descartes), Esther PEROUMAL (Adj Tec; Sorbonne Univ).

Contact details: 33 1 44 27 90 85, Email: mehdi.bennaci@crc.jussieu.fr

Laboratory website: http://www.ici.upmc.fr

Other links: http://www.immunoscore.org


Publications

  • Angelova M, Mlecnik B, Vasaturo A, Bindea G, Fredriksen T, Lafontaine L, Buttard B, Morgand E, Bruni D, Jouret-Mourin A, Hubert C, Kartheuser A, Humblet Y, Ceccarelli M, Syed N, Marincola FM, Bedognetti D, Van den Eynde M, Galon J. Evolution of Metastases in Space and Time under Immune Selection. Cell. 2018 Oct 18;175(3):751-765.e16. doi: 10.1016/j.cell.2018.09.018. Epub 2018 Oct 11.
  • Pagès F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, Lugli A, Zlobec I, Rau TT, Berger MD, Nagtegaal ID, Vink-Börger E, Hartmann A, Geppert C, Kolwelter J, Merkel S, Grützmann R, Van den Eynde M, Jouret-Mourin A, Kartheuser A, Léonard D, Remue C, Wang JY, Bavi P, Roehrl MHA, Ohashi PS, Nguyen LT, Han S, MacGregor HL, Hafezi-Bakhtiari S, Wouters BG, Masucci GV, Andersson EK, Zavadova E, Vocka M, Spacek J, Petruzelka L, Konopasek B, Dundr P, Skalova H, Nemejcova K, Botti G, Tatangelo F, Delrio P, Ciliberto G, Maio M, Laghi L, Grizzi F, Fredriksen T, Buttard B, Angelova M, Vasaturo A, Maby P, Church SE, Angell HK, Lafontaine L, Bruni D, El Sissy C, Haicheur N, Kirilovsky A, Berger A, Lagorce C, Meyers JP, Paustian C, Feng Z, Ballesteros-Merino C, Dijkstra J, van de Water C, van Lent-van Vliet S, Knijn N, Mușină AM, Scripcariu DV, Popivanova B, Xu M, Fujita T, Hazama S, Suzuki N, Nagano H, Okuno K, Torigoe T, Sato N, Furuhata T, Takemasa I, Itoh K, Patel PS, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Sargent DJ, Fox BA, Galon J. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018 May 26;391(10135):2128-2139. doi: 10.1016/S0140-6736(18)30789-X. Epub 2018 May 10.
  • Mlecnik B, Van den Eynde M, Bindea G, Church SE, Vasaturo A, Fredriksen T, Lafontaine L, Haicheur N, Marliot F, Debetancourt D, Pairet G, Jouret-Mourin A, Gigot JF, Hubert C, Danse E, Dragean C, Carrasco J, Humblet Y, Valge-Archer V, Berger A, Pagès F, Machiels JP, Galon J. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival. J Natl Cancer Inst. 2018 Jan 1;110(1). doi: 10.1093/jnci/djx123.
  • Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D, Church SE, Lafontaine L, Fischer M, Fredriksen T, Sasso M, Bilocq AM, Kirilovsky A, Obenauf AC, Hamieh M, Berger A, Bruneval P, Tuech JJ, Sabourin JC, Le Pessot F, Mauillon J, Rafii A, Laurent-Puig P, Speicher MR, Trajanoski Z, Michel P, Sesboüe R, Frebourg T, Pagès F, Valge-Archer V, Latouche JB, Galon J. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity. 2016 Mar 15;44(3):698-711. doi: 10.1016/j.immuni.2016.02.025.
  • Galon J*, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc P-H, Trajanoski Z, Fridman W-H, Pages F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006.313:1960-4

Lien vers View all publications 

Les Outils