Gregoire Lauvau, Ph.D.

Immune effector cell differentiation & protective host responses against microbial pathogens and tumors in vivo

We have three funded research themes in the laboratory that focus on:

1. The functional differentiation of naive and memory CD8+ T cells: we have built advanced experimental systems in mice to assess the roles of cognate antigen in the functional fates of memory CD8 T cells and their ability to mediate host protection. Our goal is to provide a comprehensive understanding of i) how to generate functionally and epigenetically distinct memory CD8 T cells and ii) how to harness memory CD8 T cell protective mechanisms to the benefit of the host for new T cell therapies.
2. Anti-tumor immunity: we are using and characterizing a novel mammary stem-cell based model of breast cancer in which several clinically relevant mutations have been introduced. This model mimics several key aspects of highly aggressive human breast cancers. We investigate mechanisms of immune escape and anti-tumor therapies. We are also exploring the immune response in the context of acute T cell lymphomas in HTLV1+ patients,
3. Immunity to malaria: we investigate i) the role of a subset of circulating cytolytic memory CD4 T cells we reported are expanded in Malawian patients clinically protected against Plasmodium falciparum using cytometry by time of flight (CyTOF) and single cell analyses. We are exploring the antigen specificity of these cells and developing mouse models to further characterize their functions and ability to protect against this number one killer parasite worldwide.
   
   Our laboratory develops multiple tools (recombinant pathogens, mice, T cell engineering), as well as cutting edge approaches that include transcriptomic, single cell transcriptomics, lentiviral engineering, epigenetic and intravital microscopy in close collaboration with other groups at Einstein. Our overall goal is to improve our fine understanding of the factors that orchestrate antimicrobial and antitumoral host protective immune responses in vivo. We believe that our work will contribute to more rationale design of immune cell-mediated preventative and therapeutic strategies.

Current laboratory members:

• Nicole Couturier, Ph.D. Student
• Abhishek Dubey, Ph.D. Student
• Jennifer Enright, Ph.D. Student
• Victory Iheanyichukwu, Ph.D. Student
• Richard Garcia-Betancourt, Ph.D., Postdoctoral Fellow
• Deepti Maheshwari, Ph.D. Postdoctoral Fellow

1. Boutet M., Nishitani K., Erler P., Couturier N., Zhang Z., Militello, A.M., Coutinho De Miranda, M., Barbieux E., Guillen E., Suzuki M., Sparano, J., Montagna, C., Guo, W* and Lauvau G.* Mutations in MLL3 promote breast cancer progression via HIF1a-dependent recruitment and differentiation of regulatory T cells into tumors. Immunity 2025,58(8):2035-2053.
2. Furtado R.*, Paul M.*, Zhang J., Sung J., Karell P., Kim RS., Caillat-Zucman S., Liang L., Felgner P., Bauleni A., Gama S., Buchwald A., Taylor T., Seydel K., Laufer M, Delahaye F., Daily J.* and G. Lauvau*. Cytolytic memory CD4+ T cell clones are expanded during Plasmodium falciparum infection. Nature Communications 2023, 14: 7726.
3. Liu Y., John P., Nishitani K., Cui J. Nishimura C. D., Christin J., Couturier N., Ren X., Wei, Y., Pulanco M.C., Galbo P.M. Jr., Zhang X., Fu,W., Cui W., Bartholdy B. A., Zheng D., Lauvau G., Fineberg S., Oktay M.H., Zang X. and W. Guo. A SOX9-B7x axis safeguards dedifferentiated tumor cells from immune surveillance to drive breast cancer progression. Developmental Cell 2023, 58:2700-2717.
4. Moore-Fried J., Paul M., Jing Z., Fooksman D.* and G. Lauvau*. CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice. eLife 2022, 11:e78873.
5. Chin S.S.*, Guillen E.*, Chorro L., Achar S., Ng K., Oberle S., Alfei F., Zehn D., Altan-Bonnet G., Delahaye F.* and G. Lauvau*. T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling. Nature Communications 2022, 13: 2240.
6. Boutet M., Benet Z., Delahaye F., Guillen E., Koch C., M’Homa Soudja S., Zehn D., Fooksman D. and G. Lauvau. Memory CD8+ T cells mediate early pathogen-specific protection via localized delivery of chemokines and IFNg to clusters of monocytes. Science Advances 2021, 7(36):eabf9975.
7. Furtado, R., Chorro L., Zimmerman N., Guillen E., Spaulding E., Chin S.S., Daily J.P. and G. Lauvau. Blockade of LAG-3 in PD-L1-deficient Mice Enhances Clearance of Blood Stage Malaria independently of humoral responses. Frontiers in Immunology 2021, 11:576743. PMC7840658
8. Clement CC, D'Alessandro A, Thangaswamy S, Chalmers S, Furtado R, Spada S, Mondanelli G, Ianni F, Gehrke S, Gargaro M, Manni G, Cara LCL, Runge P, Tsai WL, Karaman S, Arasa J, Fernandez-Rodriguez R, Beck A, Macchiarulo A, Gadina M, Halin C, Fallarino F, Skobe M, Veldhoen M, Moretti S, Formenti S, Demaria S, Soni RK, Galarini R, Sardella R, Lauvau G, Putterman C, Alitalo K, Grohmann U, Santambrogio L. 3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine. Nature Communications 2021, 12(1):4447. PMC8295276
9. Chorro L., Suzuki M., Williams T.M., Snapp E.L., Odagiu L., Labrecque N. and G. Lauvau. Interleukin 2 Modulates Functional Regulatory T Cell Epigenetic Landscape. Nature Communications 2018, 18;9(1):5368.
10. Spaulding E., D. Fooksman, A. Saidi, C. Feintuch, B. Reizis, J. Daily and G. Lauvau. STING-Licensed Macrophages Prime Type I IFN Production by Plasmacytoid Dendritic Cells in the Bone Marrow during Severe Plasmodium yoelii Malaria. PLoS Pathogens 2016, 12(10):e1005975.
11. Menezes S, Melandri D, Anselmi G, Perchet T, Loschko J, Dubrot J, Patel R, Gautier EL, Hugues S, Longhi MP, Henry JY, Quezada SA, Lauvau G, Lennon-Duménil AM, Gutiérrez-Martínez E, Bessis A, Gomez-Perdiguero E, Jacome-Galarza CE, Garner H, Geissmann F, Golub R, Nussenzweig MC, Guermonprez P. The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells. Immunity 2016, 45(6):1205-1218.
12. Subramaniam K.S., Spaulding E., Ivan E., Mutimura E., Kim R.S., Liu X., Dong C., Feintuch C.M., Zhang X., Anastos K., Lauvau G. and Daily J.P. The T cell inhibitory molecule BTNL2 is upregulated in mild Plasmodium falciparum infection and is protective during experimental cerebral malaria. J Infect Dis 2015, Apr 15. pii: jiv217..
13. Anne L. Ruiz,, Saidi M’Homa Soudja, Cyril Deceneux, Grégoire Lauvau and Julien C. Marie. NK1.1+ CD8+ T Cells Escape TGFbeta control and Contribute to Early Microbial Pathogen response. 2014. Nature Communications 2014, 5:5150.
14. Soudja M’Homa S., Jacob E., Chandrabos C., M. Veenstra, Palliser D. and G. Lauvau. Memory T cell-derived IFN-g instructs potent innate cell activation for protective immunity. Immunity 2014, 40(6):974-88.
15. Soudja M’Homa S., Ruiz A. L., Marie J. C., and G. Lauvau. Inflammatory monocytes switch on memory CD8+ T and innate NK lymphocytes during microbial pathogens invasion. Immunity 2012, 37(3):549-62.
16. Narni-Mancinelli E., Soudja M’Homa S., Crozat K., Dalod M., Gounon P., Geissmann F. and G. Lauvau. Inflammatory monocytes and neutrophils are licensed to kill during Memory responses in vivo. PLoS Pathogens 2011, Vol 7(12):e1002457.
17. Auffray C.*, D. K. Fogg*, E. Narni-Mancinelli*, B. Senechal, C. Touillet, N. Saederup, J. Leemput, K. Bigot, L. Campisi, M. Abitbol, T. Molina 1, I. Charo, D. A. Hume, A. Cumano, G. Lauvau and F. Geissmann. CX3CR1+ CD115+ CD135+ common macrophage/DC precursor (MDP) and the role of CX3CR1 in their response to inflammation. J Exp Med 2009, 206: 595-606.
18. Narni-Mancinelli E., L. Campisi, D. Bassand, J. Cazareth, P. Gounon, N. Glaichenhausand G. Lauvau. Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes. J Exp Med 2007, 204: 2075-2087.
19. Auffray, C., D. K. Fogg, Meriem Garfa, G. Elain, O. Join-Lambert, S. Kayal, S. Sarnacki, A. Cumano, G. Lauvau and F. Geissmann. Patrolling blood monocytes that monitor blood vessels and tissues for damage and infection. Science 2007, 317, 666-70.

Review Articles/Chapters:

1. Lauvau, G and S. A. Porcelli. Chapter 20: Innate Immunity, Kelley & Firestein's Textbook of Rheumatology 11e, 2020.
2. Lauvau, G., M. Boutet, T.M. Williams, M. Shu Shien Chin and L. Chorro. Memory CD8+ T Cells: Innate-Like Sensors and Orchestrators of Protection. Trends in Immunology 2016, 37(6):375-85.
3. Lauvau, G. and S. Goriely. Memory CD8 T cells: Orchestrators and Key Players of Innate Immunity? PLoS Pathogens 2016, 12(9):e1005722.
4. Lauvau G., Loke P., Holh T.M. Monocyte Mediated Defense Against Pathogenic Microbes. Seminars in Immunology 2016, 27(6):397-409.
5. Lauvau G., M’Homa Soudja S., Chorro L. T cell Memory. Encyclopedia of Medical Immunology, I.R. Mackay, N.R. Rose (eds.), Springer Science 2013, DOI 10.1007/978-0-387-84828-0.
6. Geissmann F., C. Auffray, R. Palframan, C. Wirrig, A. Ciocca, L. Campisi, E. Narni-Mancinelli, and G. Lauvau. Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T cell responses. Immunology and Cell Biology 2008, 86:398-408.