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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) DNA microarrays, and (iii) Software for complex analysis and visualization of the data, such as ClueGO and CluePedia.

Le laboratoire de recherche est localisé au Centre de Recherche des Cordeliers (Paris), et nous avons crée un laboratoire translationel, localisé à la plateforme d’immunomonitoring de l'Hôpital Européen Georges Pompidou, (Paris).

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 (Galon et al. Cancer Res 2007). 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, Science Transl Med 2014).

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

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).

Bioinformatics :

We have developed novel bioinformatics software, including ClueGO and CluPedia.

More information about these software can be found at : http://www.ici.upmc.fr

 

  • Bindea G, et al. Bioinformatics. 2009
  • Bindea G, et al. Bioinformatics. 2009
    ClueGO Software downloaded >24,000 times worldwide (top1) 
  • Bindea G, et al. Bioinformatics. 2013
    CluePedia Software downloaded >12,000 times worldwide (top5)

 

 HalioDx – Immuno-Oncology Diagnostic company

 
Co-founder 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.


Dr. Jérôme Galon – co-founder of HalioDx

 

 Team Leader: Jérome GALON (DR1)

Team Members : Anne BERGER (Pr), Christine LAGORCE (Dr), Franck PAGES (Pr), Guy ZEITOUN (Pr)
Samira BERRY (Tec), Bénédicte BUTTARD (Eng), Tessa FREDRIKSEN (Eng),  Lucie LAFONTAINE (Tech), Florence MARLIOT (Eng).
Mihaela ANGELOVA (Doc), Gabriela BINDEA (Post‐Doc), Pauline MABY (Post‐Doc), Bernhard MLECNIK (Post‐Doc), Marc VAN DEN EYDE (Doc), Angela VASATURO (Post-Doc).

Administration : Mehdi BENNACI, Esther PEROUMAL  

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


Selected Publications

  • Mlecnik B, Bindea G, Angell HK, Sasso MS, Obenauf AC, Fredriksen T, Lafontaine L, Bilocq AM, Kirilovsky A, Tosolini M, Waldner M, Berger A, Fridman WH, Rafii A, Valge-Archer V, Pagès F, Speicher MR, Galon J.*
    Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients.
    Science Transl. Med. 2014 Mar 19;6(228)
  • Galon J*, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, Botti G, Tatangelo F, Delrio P, Maio M, Laghi L, Grizzi F, Asslaber M, D'Arrigo C, Vidal-Vanaclocha F, Zavadova E, Chouchane L, Ohashi PS, Hafezi-Bakhtiari S, Wouters BG, Roehrl M, Nguyen L, Kawakami Y, Hazama S, Okuno K, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Wang Y, Kopetz S, Sinicrope FA, Scripcariu V, Ascierto PA, Marincola FM, Fox BA, Pagès F.
    Towards the introduction of the Immunoscore in the classification of malignant tumors.
    J Pathol. 2014 Jan;232(2):199-209.
  • Bindea G,  Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell HK, Fredriksen T, Lafontaine L, Berger A, Bruneval P, Fridman WH, Becker C, Pagès F, Speicher MR, Trajanoski Z, Galon J*
    Spatio-temporal dynamics of intratumoral cells reveal the immune landscape in human cancer
    Immunity. 2013 Oct 17;39(4):782-95.
  • Galon J*, Angell HK, Bedognetti D, and Marincola F
    The continuum of cancer immunosurveillance: prognostic, predictive and mechanistic signatures
    Immunity. 2013 July 39(1), 11-26 (IF: 20.72)
  • 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
  • Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J*
    Effector memory T cells, early metastasis, and survival in colorectal cancer.
    N Engl J Med. 2005 Dec 22;353(25):2654-66.

View all publications

Link to PubMed

 

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