CD74 supports accumulation and function of regulatory T cells in tumors

Elisa Bonnin, Maria Rodrigo Riestra, Federico Marziali, Rafael Mena Osuna, Jordan Denizeau, Mathieu Maurin, Juan Jose Saez, Mabel Jouve, Pierre-Emmanuel Bonté, Wilfrid Richer, Fabien Nevo, Sebastien Lemoine, Nicolas Girard, Marine Lefevre, Edith Borcoman, Anne Vincent-Salomon, Sylvain Baulande, Helene D. Moreau, Christine Sedlik, Claire Hivroz, Ana-Maria Lennon-Duménil, Jimena Tosello Boari () and Eliane Piaggio ()
Additional contact information
Elisa Bonnin: PSL University, Institut Curie Research Center
Maria Rodrigo Riestra: PSL University, Institut Curie Research Center
Federico Marziali: PSL University, Institut Curie Research Center
Rafael Mena Osuna: PSL University, Institut Curie Research Center
Jordan Denizeau: PSL University, Institut Curie Research Center
Mathieu Maurin: PSL University, Institut Curie Research Center
Juan Jose Saez: PSL University, Institut Curie Research Center
Mabel Jouve: PSL University, Institut Curie Research Center
Pierre-Emmanuel Bonté: PSL University, Institut Curie Research Center
Wilfrid Richer: PSL University, Institut Curie Research Center
Fabien Nevo: Egle Therapeutics
Sebastien Lemoine: Egle Therapeutics
Nicolas Girard: PSL University, Institut Curie Research Center
Marine Lefevre: Institut Mutualiste Montsouris
Edith Borcoman: Institut Curie
Anne Vincent-Salomon: Institut Curie
Sylvain Baulande: PSL Research University, Institut Curie Research Center
Helene D. Moreau: PSL University, Institut Curie Research Center
Christine Sedlik: PSL University, Institut Curie Research Center
Claire Hivroz: PSL University, Institut Curie Research Center
Ana-Maria Lennon-Duménil: PSL University, Institut Curie Research Center
Jimena Tosello Boari: PSL University, Institut Curie Research Center
Eliane Piaggio: PSL University, Institut Curie Research Center

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Regulatory T cells (Tregs) are plastic cells playing a pivotal role in the maintenance of immune homeostasis. Tregs actively adapt to the microenvironment where they reside; as a consequence, their molecular and functional profiles differ among tissues and pathologies. In tumors, the features acquired by Tregs remains poorly characterized. Here, we observe that human tumor-infiltrating Tregs selectively overexpress CD74, the MHC class II invariant chain. CD74 has been previously described as a regulator of antigen-presenting cell biology, however its function in Tregs remains unknown. CD74 genetic deletion in human primary Tregs reveals that CD74KO Tregs exhibit major defects in the organization of their actin cytoskeleton and intracellular organelles. Additionally, intratumoral CD74KO Tregs show a decreased activation, a drop in Foxp3 expression, a low accumulation in the tumor, and consistently, they are associated with accelerated tumor rejection in preclinical models in female mice. These observations are unique to tumor conditions as, at steady state, CD74KO-Treg phenotype, survival, and suppressive capacity are unaffected in vitro and in vivo. CD74 therefore emerges as a specific regulator of tumor-infiltrating Tregs and as a target to interfere with Treg anti-tumor activity.

Date: 2024
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DOI: 10.1038/s41467-024-47981-3

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