Group members
Team photo
Project
Cutaneous melanoma is a major public health concern, affecting approximately 8,000 to 10,000 individuals each year in France. It is regarded as one of the most immunogenic solid tumors, and the presence of CD8⁺ T cells infiltrating primary tumors has been strongly associated with a favorable prognosis. In recent years, immune checkpoint inhibitors targeting the T-cell inhibitory receptors CTLA-4 and PD-1, designed to restore the function of exhausted tumor-specific T cells, have revolutionized the treatment of metastatic cutaneous melanoma. However, clinical outcomes in terms of overall survival and therapeutic response remain highly heterogeneous, underscoring the need to further elucidate the mechanisms of tumor immune escape and to identify new molecular targets.
Enzymes involved in amino acid catabolism have emerged as promising targets in cancer therapy. In particular, our team has demonstrated the pro-tumoral role of interleukin-4-induced gene 1 (IL4I1) in melanoma, thereby strengthening the rationale for targeting this phenylalanine oxidase in combinatorial therapeutic strategies (Bod et al., 2017; Ramspott et al., 2018; Bekkat et al., 2024; Seradj et al., 2026). We are currently investigating the impact of IL4I1 on the immune response during the early stages of tumor development using spontaneous metastatic melanoma models, including transgenic mice expressing the human RET oncogene with either wild-type or inactivated IL4I1. In parallel, we are assessing whether IL4I1 expression constitutes a relevant prognostic marker and/or a determinant of resistance to immunotherapy in melanoma patients enrolled in a clinical trial conducted in collaboration with clinicians from Cochin and Avicenne hospitals (ClinicalTrials.gov Identifier: NCT04253080).
In conclusion, our work aims to improve the understanding of the complex interactions between tumor cells and the immune microenvironment and to contribute to the development of innovative therapeutic strategies for cancer patients.
Fundings
News of the group
Wellcome back to Saniya for a 3 year post-doc
Congratulations to Saniya Kari who received a grant from Fondation de France in July 2024.
Saniya will evaluate the contribution of IL4I1 on the resistance to anti-PD1 in melanoma patients.
A huge thanks to the Fondation de France for financial support and patients for their contribution to the project.
The team is well-represented at the French Immunology Society, 2025
Anna (PhD student) and Saniya (Post-doctorant) in my group
Mattia from the Frederic Pendino's group
Adrian from the Nadege Bercovici's group, who received a price for his poster.
Main publications
IL4I1
- Seradj M, Kari S, Llebaria Fabrias A, Rouault A, Herrmann A, Lengagne R, Kato M, Castellano F, Molinier-Frenkel V, Llebaria A, Bercovici N and A Prévost-Blondel. Conditional IL4I1 inactivation triggers tumor-associated macrophage reprogramming and CD8+ T cell reactivation. Cancer Immunol Res. CIR-24-1159. 2026.PMID: 41537775
- Bekkat F, Seradj M, Lengagne R, Chew S, Kato M, Lucas B, Castellano F, Molinier-Frenkel V, Richard Y, A Prévost-Blondel. Up-regulation of IL4-induced gene 1 enzyme by B2 cells during melanoma progression impairs their anti-tumor properties. Eur J Immunol. 2024 e2350615. 2021. PMID: 38400692
- Castellano F, Prévost-Blondel A, Cohen JL, Molinier-Frenkel V. What role for AHR activation in IL4I1-mediated immunosuppression ? Oncoimmunol. Vol.10(1), e1924500. 2021. PMID: 34026337
- Puiffe ML, Dupont A, Sako N, Gatineau J, Cohen J, Mestivier D, Le Bon A, Prévost-Blondel A, Castellano F and Molinier-Frenkel V. IL4I1 accelerates the expansion of effector CD8+ T cells at the expense of memory precursors by increasing the threshold of T cell activation. Front. Immunol. 11:600012. 2020. PMID: 33343572
- Prévost-Blondel A, Richard Y. IL4-induced gene 1 as an emerging regulator of B-cell biology and its role in cutaneous melanoma? Crit Rev Immunol. 39(1):39-57. 2019. PMID: 31679193
- Bod L, Douguet L, Auffray, C, Lengagne R, Bekkat F, Rondeau E, Molinier-Frenkel V, Castellano F, Richard Y and Prévost-Blondel A. IL4-induced gene 1 : a negative immune checkpoint controlling B cell differentiation and activation. J Immunol. 200(3):1027-1038. 2018. PMID: 29288206
- Bod L, Lengagne R, Wroebel L, Ramspott JP, Kato M, Castellano F, Avril MF, Molinier-Frenkel V, and Prévost-Blondel A. IL4-induced gene 1 promotes tumor growth and modulates the tumor microenvironment in a spontaneous model of melanoma. Oncoimmunol. 6(3):e1278331. 2017. PMID: 28405502
Human melanoma
- Ramspott JP, Bekkat F, Bod L, Maryline Favier M, Terris B, Salomon A, Djerroudi L, Zaenker KS, Richard Y, Molinier-Frenkel V, Castellano F, Avril M-F and Prévost-Blondel A. Emerging role of IL-4 induced gene 1 as a prognostic biomarker affecting the local T cell response in human cutaneous melanoma. J Invest Dermatol 138(12):2625-2634. 2018. PMID: 30048651
- Chapon M, Randriamampita C, Maubec E, Badoual C, Fouquet S, Wang S-F, Marinho E, Farhi D, Garcette M, Jacobelli S, Rouquette A, Carlotti A, Girod A, Prévost-Blondel A, Trautmann A, Avril MF, N Bercovici. Progressive upregulation of PD1 in primary and metastatic melanoma associated with blunted TCR-signalling in infiltrating T lymphocytes. J Invest Dermatol 131:1300-07. 2011. PMID: 21346771
- Wang SF, Fouquet S, Chapon M, Salmon H, Regnier F, Labroquère K, Badoual C, Damotte D, Validir P, Maubec E, Barry N, Cazes A, Vieillefond A, Garcette M, Dieu-Nosjean MC, Zerbib M, Barthes F, Avril MF, Prevost-Blondel A, Randriamampita C, Trautmann A, N Bercovici. Early T cell signalling is reversibly altered in T lymphocytes infiltrating human tumors. Plos One. 6:e17621. 2011. PMID: 21408177
- Nardin A, Wong WC, Tow C, Molina T, Tissier F, Audebourg A, Garcette M, Caignard A, Avril MF, Abastado JP, A Prévost-Blondel. Dacarbazine promotes stromal remodeling and lymphocyte infiltration in cutaneous melanoma lesions. J Invest Dermatol 131(9):1896-905. 2011. PMID: 21654834
Melanoma models: RET mice and MeLiM swine
- Blanc F, Bertho N, Piton G, Leplat J-J, Egidy G, Bourneuf E, Vincent-Naulleau S, A Prévost-Blondel. Deciphering the immune reaction leading to spontaneous melanoma regression: initial role of MHCII+ CD163- macrophages. Cancer Immunol Immunother. 72(11):3507-3521. 2023. PMID: 37526660
- Blanc F, A Prévost-Blondel, G Piton, E Bouguyon, J-J Leplat, F Andréoletti, G Egidy-Maskos, E Bourneuf, N Bertho, S Vincent-Naulleau. The composition of circulating leukocytes varies with age and melanoma onset in the MeLiM pig biomedical model. Front. Immunol. 00291 eCollection. 2020. PMID: 32180771
- Pommier A, Audemard A,Durand A, Lengagne R, Delpoux A, Martin B, Douguet L, Le Campion A, Kato M, Avril MF, Auffray C, Lucas B, Prevost-Blondel A. Inflammatory monocytes are potent anti-tumor effectors controlled by regulatory CD4+ T cells. PNAS. 110(32):13085-13090. 2013. PMID: 23878221
- Toh B, Wang X, Keeble J, Jing Sim W, Khoo K, Wong WC, Kato M, Prevost-Blondel A, Thiery JP, JP Abastado. Mesenchymal Transition and Dissemination of Cancer Cells is driven by Myeloid-Derived Suppressor Cells Infiltrating the Primary Tumor. PLoS Biol. 9(9):e1001162. 2011. PMID: 21980263
- Lengagne R, Pommier A, Caron J, Douguet L, Garcette M, Kato M, Avril MF, Abastado JP, Bercovici N, Lucas B, Prévost-Blondel A. T cells contribute to tumor progression by favoring pro-tumoral properties of intra-tumoral myeloid cells in a mouse model for spontaneous melanoma. Plos One. 6:e20235. 2011. PMID: 21633700
- Eyles J, Puaux AL, Wang X, Toh B, Prakash C, Hong M, Tan TG, Zheng L, Ong LC, Jin Y, Kato M, Prévost-Blondel A, Chow P, Yang H, Abastado JP. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J. Clin. Invest. 120(6):2030-9. 2010. PMID: 20501944
- Lengagne R, Graff-Dubois S, Garcette M, Renia L, Kato M, Guillet JG, Engelhard VH, Avril MF, Abastado JP, Prévost-Blondel A. Distinct role for CD8 T cells toward cutaneous tumors and visceral metastases. J. Immunol. 180:130-7. 2008. PMID: 18097012
- Lengagne R, FA Le Gal, M Garcette, L Fiette, P Ave, M Kato, JP Briand, C Massot, I Nakashima, L Rénia, JG Guillet, A Prévost-Blondel. Spontaneous vitiligo in an animal model for human melanoma: Role of tumor-specific CD8+ T cells. Cancer Res. 64:1496-1501. 2004. PMID: 14973052
Collaborations on melanoma
- Canali MM, Guyot M, Simon T, Daoudlarian D, Chabry J, Panzolini C, Petit-Paitel A, Hypolite N, Nicolas S, Bourdely P, Schmid-Antomarchi H, Schmid-Alliana A, Soria J, Karimdjee Soilihi B, Hofman P, Prevost-Blondel A, Kato M, Mougneau E, Glaichenhaus N, Blancou P. Environmental signals perceived by the brain abate pro-metastatic monocytes by dampening glucocorticoids receptor signaling. Cancer Cell Int. 23(1):15. 2023. PMID 36726173
- Jacquelot N, Yamazaki T, Roberti MP, Andrews MC, Verlingue L, Ferrere G, Duong C, Becharef S, Vétizou M, Daillère R, Messaoudene M, Enot D, Stoll G, Ugel S, Marigo I, Ngiow S, Marabelle A, Prévost-Blondel A, Gaudreau PO, Gopalakrishnan V, Eggermont A, Opolon P, Klein C, Madonna G, Ascierto P, Sucker A, Schadendorf D, Smyth MJ, Soria JC, Kroemer G, Bronte V, Wargo J, and Zitvogel L. Sustained Type I IFN signaling as a mechanism of resistance to PD-1 blockade. Cell Res. 29(10):846-861. 2019. PMID: 31481761
- Végran F, Berger H, Boidot R, Mignot G, Bruchard M, Dosset M, Chalmin F, Rébé C, Dérangère V, Ryffel B, Kato M, Prévost-Blondel A, Ghiringhelli F and Apetoh L. The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells. Nat Immunol. 15(8):758-66. 2014. PMID: 24973819
- Terme M, Ullrich E, Aymeric L, Meinhardt K, Coudert J, Desbois François Ghiringhelli , Viaud S,Ryffel B, Yagita H, Chen L, Mecheri S, Kaplanski G, Prévost-Blondel A, Kato M, Schultze JL, Tartour E, Kroemer G, Degli-Esposti M, Chaput N, Zitvogel, L. Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells. Cancer Res. 72(11):2757-67. 2012. PMID: 22427351
- Chauvin JM, Larrieu P, Sarrabayrouse G, Prévost-Blondel A, Lengagne R, Desfrançois J, Labarriere N, Jotereau F. HLA anchor optimization of the Melan-A-HLA-A2 epitope within a long peptide is required for efficient cross-priming of human tumor-reactive T cells. J Immunol. 188(5):2102-10. 2012. PMID: 22291187
Alumni
- Stéphanie Graff-Dubois, former Post-doctoral fellow Cancéropole (2006-2007) is Professor in Immunology at Sorbonne University
- Arnaud Pommier. former PhD student (2009-2012) is engineer, University of Reims.
- Fany Blanc, former Post-doctoral fellow INCA (2012-2015), is engineer, INRA Jouy en Josas.
- Laetitia Douguet, former Master and PhD student (2010-2015) is Senior scientist, immuno-oncology project manager, TheraVectys, Paris
- Lloyd Bod, former Master, PhD student and Post-doctoral fellow (2012-2017) is Professor assistant, Team leader at Harvard Medical School (Boston).
- Jan-Philipp Ramspott, former ERASMUS MD student (2015-2016) is MD, in Hospital Münster.
- Fériel Bekkat, former Master and PhD student (2017-2021). Consultant in health innovation, Paris.
- Samantha Chew, former Post-doctoral fellow INCA (2019-2021). A* STAR Institute, Singapore.
- Mubashira Tariq, former Post-doctoral fellow INCA (2022-2023).
- Juliette Bouchet, former Master (2024).
- Malvina Seradj, former PhD student (2021-2024) is Post-doctoral fellow at Institute of Cancer Research (London)
- Marie Malige, former Master (2025).
- Anna Llebaria Fabrias, Former PhD student (2022-2025) is working in Institute of Advanced Chemistry in Barcelona.
