Skip to Main content Skip to Navigation
Journal articles

A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system

Abstract : Mice reconstituted with a human immune system and bearing human tumors represent a promising model for developing novel cancer immunotherapies. Here, we used mass cytometry and multi-parametric flow cytometry to characterize human leukocytes infiltrating a human breast cancer tumor model in immunocompromised NOD.SCID.γc-null mice reconstituted with a human immune system and compared it to samples of breast cancer patients. We observed highly activated human CD4+ and CD8+ T cells in the tumor, as well as minor subsets of innate immune cells in both settings. We also report that ICOS+ CD4+ regulatory T cells (Treg) were enriched in the tumor relative to the periphery in humanized mice and patients, providing a target to affect Treg and tumor growth. Indeed, administration of a neutralizing mAb to human ICOS reduced Treg proportions and numbers and improved CD4 + T cell proliferation in humanized mice. Moreover, a combination of the anti-ICOS mAb with cyclophosphamide reduced tumor growth, and that was associated with an improved CD8 to Treg ratio. Depletion of human CD8+ T cells or of murine myeloid cells marginally affected the effect of the combination therapy. Altogether, our results indicate that a combination of anti-ICOS mAb and chemotherapy controls tumor growth in humanized mice, opening new perspectives for the treatment of breast cancer.
Document type :
Journal articles
Complete list of metadatas

Cited literature [53 references]  Display  Hide  Download

https://hal.sorbonne-universite.fr/hal-02131378
Contributor : Gestionnaire Hal-Su <>
Submitted on : Thursday, May 16, 2019 - 12:18:41 PM
Last modification on : Monday, December 14, 2020 - 9:46:49 AM

File

A novel combination of chemoth...
Publication funded by an institution

Identifiers

Citation

Aude Burlion, Rodrigo Ramos, Pukar Kc, Kelhia Sendeyo, Aurélien Corneau, et al.. A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system. OncoImmunology, Taylor & Francis, 2019, 8 (7), pp.1596005. ⟨10.1080/2162402X.2019.1596005⟩. ⟨hal-02131378⟩

Share

Metrics

Record views

610

Files downloads

1061