The small GTPase Rab32 expressed in XCR1+ type 1 DCs contributes to efficient in vivo cross-priming of CD8⁺ T cells against cell-associated antigens
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The small GTPase Rab32 expressed in XCR1+ type 1 DCs contributes to efficient in vivo cross-priming of CD8⁺ T cells against cell-associated antigens

Naman Tandon
1,*
,
Enric Gutiérrez-Martínez
2,*
,
Pierre Bourdely
3
,
Giorgio Anselmi
4
,
Jordan Denisot
5
,
Yohan Gerber-Ferder
5
,
Julie Helft
6
,
Marcelle Bens
1
,
Loredana Saveanu
1
,
Pierre Guermonprez
7,*
*Correspondence to: Pierre Guermonprez, Laboratory of Dendritic cells and adaptive immunity, Department of Immunology, Université de Paris, Institut Pasteur, CNRS UM3738, Paris 75015, France. E-mail: pierre.guermonprez@pasteur.fr
Naman Tandon, Centre de recherche sur l'inflammation, Université de Paris, INSERM U1149, CNRS, ERL8252, Paris F-75018, France. E-mail: namannt@gmail.com
Enric Gutiérrez-Martínez, Centre for Inflammation Biology and Cancer Immunology, The Peter Gorer Department of Immunobiology, King’s College London, London SE1 9RT, UK. E-mail: enricgutierrez@gmail.com
Myeloid Cells. 2026;1:202617. 10.70401/mc.2026.0015
Received: July 09, 2026Accepted: November 09, 2026Published: November 10, 2026
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This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Aims: Type 1 conventional dendritic cells (cDC1s) are critical for initiating adaptive immune responses through the cross-priming of CD8⁺ T cells against antigens from tumor or virus-infected cells. This function depends on specialized cross-presentation pathways that allow cDC1s to process phagocytosed cell debris and present peptide–MHC I complexes and efficient interaction between cDC1 and CD8+ T cells. In this study, we aim at evaluating the role of Rab32, a small GTPase highly expressed in cDC1s in the cross-priming pathway.

Methods: We have characterized cDC1 from Rab32 deficient mice and evaluated the ability of Rab32 deficient dendritic cells to activate CD8+ T cell responses against cell-associated antigens, including tumor-associated antigens.

Results: While cDC1s from Rab32-deficient mice develop normally and can respond to maturation signals, their capacity to activate CD8⁺ T cells in vivo is impaired. Notably, Rab32-deficient cDC1s retain the ability to stimulate high affinity TCR transgenic CD8⁺ T cells ex vivo using both cell-associated antigens and MHC I-binding peptides of varying affinity. However, in vivo, Rab32 is essential for effective CD8⁺ T cell responses to cell-associated antigens, and plays a role outside of the T cell compartment. Importantly, Rab32-mediated cross-priming is required for the efficient expansion of tumor-specific CD8⁺ T cells into solid tumors.

Conclusion: These findings underscore a critical role for Rab32 in the cross-priming of cell associated antigens.

Keywords

Dendritic cells, MHCI, cross-priming, CD8+ T cells

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Tandon N, Gutiérrez-Martínez E, Bourdely P, Anselmi G, Denisot J, Gerber-Ferder Y, et al. The small GTPase Rab32 expressed in XCR1+ type 1 DCs contributes to efficient in vivo cross-priming of CD8⁺ T cells against cell-associated antigens. Myeloid Cells. 2026;1:202617. https://doi.org/10.70401/mc.2026.0015

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