Translational Immunotherapy

Eliane Piaggio

Eliane Piaggio PhD, DR2 INSERM, Chef d'équipe Tel:

Cancer immunotherapy can be viewed as “The Breakthrough of 2013”, switching cancer treatment from targeting the tumor to targeting the immune system.

The blockade of immune checkpoints with antibodies (Ab) anti-CTLA-4, anti-PD1 and anti-PD-L1, has given impressive clinical results and manageable safety profiles. As reports of therapeutic efficacy with checkpoint inhibitors extend from metastatic melanoma, renal cell carcinoma and lung cancer to other tumors, the opportunity arises for other type of cancer patients, including breast, ovarian, head & neck (H&N), and paediatric tumours to benefit from these new therapies. There is no doubt that in the upcoming years, immunotherapy will represent a substantial part of the therapeutic arsenal to treat cancer.

3-  Our main research programs and achievements:

a. Immunotherapy studies based on the analysis of human tumor-draining lymph nodes (LNs).

We are performing a holistic comparison of the immune profile of invaded versus non-invaded LNs. Our aim is to identify immunomodulatory mechanisms associated to the presence of the invading tumor in the LNs, and to discover biomarkers that could guide the design of patient-tailored immune therapies. Techniques: phenotypic and functional analysis of tumor, fibroblasts, B and T, DCs and NK cells by multi-parametric flow cytometry, ELISPOT, LUMINEX, RNAseq, phage display…. We have established national and international collaborations with groups expert in each of the subpopulation studied. We have created a lymph node collection for research purposes.
One special focus is the study of tumor neoepitopes for future personalized anti-cancer vaccines.

Piaggio/Loirat

 

b. Translation of IL-2/antI-IL-2 Ab complexes immunotherapy to the clinics

The FDA has already approved high-dose IL-2 therapy for metastatic melanoma and renal carcinoma treatment. However, high-dose of IL-2 administration is highly toxic and has low efficacy. In this project, we want to use IL-2/antI-IL-2 complexes directed to CD8+ and NK T cells, in view of clinical application, as monotherapy or combined with other immunotherapies in different tumor mouse models.

c. Study immunotherapies in optimized in vivo models for cancer

To improve our understanding and to build better and more translatable in vivo mouse tumor models, we are developing humanized mouse models consisting of the transplant of patient-derived tumor xenografts into immunodeficient mice reconstituted with human immune cells (isolated from the matching patient from the draining LNs or with allogenic PBMCs or LN cells). This is a collaborative project with the Laboratory of Preclinical Investigation, LIP. The final aim is improving therapeutic effect and defining rationalized drug combinations with immune checkpoints and proprietary molecules developed by collaborators, including novel immunomodulatory approaches generated at our unit.
Also, using this model we are evaluating the role of microbiota on the response to anti-PD-1 Ab treatment.

Piaggio/Loirat 2

Key publications

Year of publication 2020

Ménoret S1,2,3, Ouisse LH1,2,3, Tesson L1,2,3, Remy S1,2,3, Usal C1,2,3, Guiffes A1,2,3, Chenouard V1,2,3, Royer PJ4, Evanno G4, Vanhove B4, Piaggio E5, Anegon I1,2,3. (2020 Apr 1)

In Vivo Analysis of Human Immune Responses in Immunodeficient Rats.

Transplantation : 104(4) : 715-723 : DOI : 10.1097/TP.0000000000003047
Lynn GM1,2, Sedlik C3,4, Baharom F5, Zhu Y6, Ramirez-Valdez RA5, Coble VL6, Tobin K5, Nichols SR6, Itzkowitz Y6, Zaidi N5, Gammon JM7, Blobel NJ5, Denizeau J3,4, de la Rochere P3,4, Francica BJ8,9, Decker B6, Maciejewski M6, Cheung J5, Yamane H5, Smelkinson MG10, Francica JR5, Laga R11, Bernstock JD6,12, Seymour LW13, Drake CG8,14, Jewell CM7, Lantz O3,4, Piaggio E3,4, Ishizuka AS5,6, Seder RA15. (2020 Mar 2)

Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens.

Nature biotechnology : 38(3) : 320-332 : DOI : 10.1038/s41587-019-0390-x
Ramos RN1,2, Rodriguez C1, Hubert M1, Ardin M1, Treilleux I3, Ries CH4, Lavergne E3, Chabaud S3, Colombe A3, Trédan O3, Guedes HG5, Laginha F5, Richer W6,7, Piaggio E6,7, Barbuto JAM2, Caux C1, Ménétrier-Caux C1, Bendriss-Vermare N1. (2020 Feb 13)

CD163+ tumor-associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes.

Clinical ans translationnal immunology : 9(2) : DOI : 10.1002/cti2.1108
De Martino M1, Tkach M2, Bruni S1, Rocha D3, Mercogliano MF1, Cenciarini ME1, Chervo MF1, Proietti CJ1, Dingli F4, Loew D4, Fernández EA3,5, Elizalde PV1, Piaggio E2, Schillaci R1. (2020 Jan 29)

Blockade of Stat3 oncogene addiction induces cellular senescence and reveals a cell-nonautonomous activity suitable for cancer immunotherapy.

Oncoimmunology. : 9(1) : DOI : 10.1080/2162402X.2020.1715767
Pol JG1,2,3,4,5, Caudana P6, Paillet J1,2,3,4,5,7, Piaggio E6,8, Kroemer G1,2,3,4,5,9,10,11. (2020 Jan 6)

Effects of interleukin-2 in immunostimulation and immunosuppression.

Journal of experimental medecine : 217(1) : DOI : 10.1084/jem.20191247

Year of publication 2019

Leruste A, Tosello J, Ramos RN, Tauziède-Espariat A, Brohard S, Han ZY, Beccaria K, Andrianteranagna M, Caudana P, Nikolic J, Chauvin C, Niborski LL, Manriquez V, Richer W, Masliah-Planchon J, Grossetête-Lalami S, Bohec M, Lameiras S, Baulande S, Pouponnot C, Coulomb A, Galmiche L, Surdez D, Servant N, Helft J, Sedlik C, Puget S, Benaroch P, Delattre O, Waterfall JJ, Piaggio E, Bourdeaut F. (2019 Dec 9)

Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors.

Cancer Cell : 36(6) : 597-612 : DOI : 10.1016/j.ccell.2019.10.008
All publications