Christophe Caux - Selected Publications#
Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature. 1992, 360:258 (45/an, H 1432)
First author of this study describing for the first time a reliable method to obtain Langerhans dendritic cells from human CD34+ hematopoietic progenitor cells. As of 2022, this paper received an average of 45 citations per year and had an H-index of 1432. This was followed by >100 publications with C Caux as co-author (half as major, first or last, author) on Dendritic Cell biology (17,800 citations). In particular C Caux was the first to demonstrate the critical role of CD40/CD40L interaction between DC and T cells (Caux C JEM. 1994: 39/yr, H 1170), and to report B70/B7-2 as the major ligand for CD28 expressed on DC (Caux C JEM. 1994 ; 11/yr, H 307) and that DC differentiate along two independent pathways from CD34+ progenitors (Caux C JEM. 1996; 28/yr, H 783).
Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Ait-Yahia S, Briere F, Zlotnik A, Lebecque S, Caux C. Selective recruitment of immature and mature DC by distinct chemokines expressed in different anatomic sites. J Exp Med. 1998, 188:373 (45/an, H 1167)
C Caux directed the work of the PhD student MC Dieu that lead to the critical discovery that immature and mature Dendritic Cells are selectively recruited by distinct chemokines expressed in different anatomic sites. A unique phenomenon explaining their route of migration from peripheral tissues where DC capture the antigens to draining lymphnode where they present antigen to T cells.
Faget J, Bendriss-Vermare N, Gobert M, Durand I, Olive D, Biota C, Bachelot T, Treilleux I, Goddard-Leon S, Lavergne E, Chabaud S, Blay JY, Caux C and Ménétrier-Caux C. ICOS-ligand expression on plasmacytoid dendritic cells supports breast cancer progression by promoting the accumulation of immunosuppressive CD4+ T cells. Cancer Research, 72(23):6130-41, 2012. (12/an 145)
C Caux directed the work on regulatory T cells infiltrating human tumors, leading to a first seminal paper in 2009 (Gobert M Cancer Res 2009; 35/an, H 522), that was followed by the discovery of the critical role of the ICOS/ICOSL interaction between dysfunctional pDC (Labidi Galy Cancer Res 2011; 12/an, H 157, Sisirak Cancer Res. 2012; 19/yr, H 222) and regulatory T cells leading to their intra-tumoral amplification and activation. This observation was patented and the licence exploited by GSK up to phase III clinical trials.
Le Mercier I, Poujol D, Sanlaville A, Sisirak S, Gobert M, Durand I, Dubois B, Treilleux I, Marvel J, Vlach J, Blay JY, Bendriss-Vermare N, Caux C *, Puisieux I * and Goutagny N* Tumor promotion by intratumoral plasmacytoid dendritic cells is reversed by TLR7L ligand treatment Cancer Res. 73:4629-4640, 2013 (12/an, 135)
C Caux directed the work of the PhD student I Le Mercier that demonstrates that the dysfunction of breast tumor infiltrating plasmacytoid Dendritic cells (pDC) that they previously reported in seminal papers (Labidi Galy Cancer Res 2011; 12/an, H 157, Sisirak Cancer Res. 2012; 19/yr, H 222) can be reverted in vivo by an agonist for the Toll-like receptor TLR-7. This work was the follow-up of previous C Caux work in other tumor models (Vicari AP JEM. 2002 ; 13/yr, H 288, Gautier G JEM. 2005 23/yr, H 430). Following this observation, TLR7-8 agonists are still pursued for therapeutic development.
Gourdin N, Bossennec M, Rodriguez C, Vigano S, Jandus C, Mâchon C, Bauché D, Faget J, Durand I, Chopin N, Tredan O, Marie J, Dubois B, Guitton J, Romero P, Caux C *, Ménétrier-Caux C *.(*co-last authorship). (2018) Autocrine Adenosine regulates tumor polyfunctional CD73+CD4+ effector T cells devoid of immune checkpoints Cancer Research July, 78(13); 3604–18. (8/an, 45)
C Caux directed this work in the framework of FP7 european program that he coordinates. The study demonstrates that a CD4 T cell effector subset characterized by CD73 expression is endowed by a unique anti-tumor TH1-17 function, and that because of CD73 expression this CD4 effector is the target of the tumor infiltrating regulatory T cells expressing up-regulated CD39 levels. Indeed CD39 and CD73 are ectonucleotidases that cooperated to catabolize extracellular ATP, an inflammatory molecule, into Adenosine a potent immunosuppressive mediator, thus leading to CD4+CD73+ T cell subset inhibition by CD39+ Treg.
Hubert M, Ardin M, Couillault C,.., Ollion V, Lopez-Maestre H, Rahmouni N,.., Rodriguez C, Sajous C, Dumont B, Doffin AC,…, Bendriss-Vermare N, Caux C*, Valladeau-Guilemond J* (*co-last authorship). cDC1 produce IFN-λ in human primary tumors and are associated with a good prognosis. Science Immunology, 5(46):eaav3942, 2020. (14/an, 54)
C Caux directed this study demonstrating for the first time that cDC1 produce IFN-λ in human primary tumors and are associated with a good prognosis. This seminal work lead to highly active work in the field of immunotherapy, analysing whether cDC1 density and localization in the tumor are associated with response to immune checkpoint blockers.
Trédan O, Ménétrier-Caux C, Ray-Coquard I, Garin G, Cropet C, Verronèse E, Bachelot T, Rebattu P, Heudel PE, Cassier P, Chabaud S, Croughs T, Dupont P, Cadore AC, Clapisson G, Delgado A, Bardin-Dit-Courageot C, Rigal C, N'Kodia A, Gilles-Afchain L, Morre M, Pérol D, Blay JY, Caux C. ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients. Ann Oncol. 26:1353-62, 2015 (5/yr, 43)
This clinical study was initiated based on C Caux translationnal work demonstrating in several reports that Lymphopenia is associated with worth clinical outcome (7 publications, 320 citations). This an example of C Caux exploratory work leading to clinical development.
Shekarian T, Sivado E, Jallas AC, Depil S, Kielbassa J, Janoueix-Lerosey I, Hutter G, Goutagny N, Bergeron C, Viari A, Valsesia-Wittmann S*, Caux C*, Marabelle A*. (*co-last authorship) Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade. Science Translational Medicine. 11(515). pii: eaat5025, 2019. (8/an, 42)
This study that C Caux co-directed with A Marabelle, is another example of successful translational work coordinated by a clinician and a scientist. This work performed in a mouse preclinical model allows to repurpose for human clinical trial a rotavirus vaccines for intratumoral immunotherapy to overcome resistance to immune checkpoint blockade.
Voissière A†, Gomez-Roca C†, Chabaud S†, Rodriguez C†, Nkodia A, Berthet J, Montane L, Bidaux AS, Treilleux I, Eberst L, Terret C, Korakis I, Garin G, Pérol D, Delord JP, Caux C , Dubois B , Ménétrier-Caux C*, Bendriss-Vermare C*, A. Cassier P*. The CSF-1R inhibitor Pexidartinib impacts DC differentiation through FLT3 inhibition and antagonizes durvalumab activity - results from a phase 1 study. Sci Transl Med in revision (MedRxiv)
This one recent example of successful achievement of C Caux, performing the immunomonitoring of investigator initiated clinical trials (>20, >420 cit) thanks to the Laboratory for Immunotherapy of Cancer of Lyon (LICL) that C Caux has set-up. This paper demonstrate that receptor tyrosine kinase inhibitors targeting CSF1R to eliminate immunosuppressive macrophage can also target other RTK such as FLT3 and C-KIT leading to depletion in most Dendritic cell populations and consequently antagonizing the therapeutic activity of immune checkpoints inhibitors.
Bonaventura P, Alcazer V, Mutez V, Tonon L, Martin J, Chuvin N, Michel E, Boulos RE, Estornes Y, Valladeau-Guilemond J, Viari A, Wang Q, Caux C, Depil S. Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy. Sci Adv. 2022 Jan 28;8(4):eabj3671. (10/yr, 20)
This study Co-directed by S Depil and C Caux is a first study to demonstrate that endogenous retroviruses are reactivated during breast tumorigenesis leading to expression of shared tumor epitopes inducing high-avidity cytotoxic T cells for cancer immunotherapy. This observation was patented and led to the reaction of the start-up ERVaccine that is developing strategies based of shared ERV epitope for anti-tumor vaccines.
érol D, Blay JY, Caux C. ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients. Ann Oncol. 26:1353-62, 2015 (5/yr, 43)
This clinical study was initiated based on C Caux translationnal work demonstrating in several reports that Lymphopenia is associated with worth clinical outcome (7 publications, 320 citations). This an example of C Caux exploratory work leading to clinical development.
Shekarian T, Sivado E, Jallas AC, Depil S, Kielbassa J, Janoueix-Lerosey I, Hutter G, Goutagny N, Bergeron C, Viari A, Valsesia-Wittmann S*, Caux C*, Marabelle A*. (*co-last authorship) Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade. Science Translational Medicine. 11(515). pii: eaat5025, 2019. (8/an, 42)
This study that C Caux co-directed with A Marabelle, is another example of successful translational work coordinated by a clinician and a scientist. This work performed in a mouse preclinical model allows to repurpose for human clinical trial a rotavirus vaccines for intratumoral immunotherapy to overcome resistance to immune checkpoint blockade.
Voissière A†, Gomez-Roca C†, Chabaud S†, Rodriguez C†, Nkodia A, Berthet J, Montane L, Bidaux AS, Treilleux I, Eberst L, Terret C, Korakis I, Garin G, Pérol D, Delord JP, Caux C , Dubois B , Ménétrier-Caux C*, Bendriss-Vermare C*, A. Cassier P*. The CSF-1R inhibitor Pexidartinib impacts DC differentiation through FLT3 inhibition and antagonizes durvalumab activity - results from a phase 1 study. Sci Transl Med in revision (MedRxiv)
This one recent example of successful achievement of C Caux, performing the immunomonitoring of investigator initiated clinical trials (>20, >420 cit) thanks to the Laboratory for Immunotherapy of Cancer of Lyon (LICL) that C Caux has set-up. This paper demonstrate that receptor tyrosine kinase inhibitors targeting CSF1R to eliminate immunosuppressive macrophage can also target other RTK such as FLT3 and C-KIT leading to depletion in most Dendritic cell populations and consequently antagonizing the therapeutic activity of immune checkpoints inhibitors.
Bonaventura P, Alcazer V, Mutez V, Tonon L, Martin J, Chuvin N, Michel E, Boulos RE, Estornes Y, Valladeau-Guilemond J, Viari A, Wang Q, Caux C, Depil S. Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy. Sci Adv. 2022 Jan 28;8(4):eabj3671. (10/yr, 20)
This study Co-directed by S Depil and C Caux is a first study to demonstrate that endogenous retroviruses are reactivated during breast tumorigenesis leading to expression of shared tumor epitopes inducing high-avidity cytotoxic T cells for cancer immunotherapy. This observation was patented and led to the reaction of the start-up ERVaccine that is developing strategies based of shared ERV epitope for anti-tumor vaccines.
