Description

Intradermal DNA vaccination generates skin-resident memory CD8 T cells with enhanced antitumor properties

Felipe Gálvez-Cancino^1#, Ernesto Lopez^1#, Camila Flores¹, Evelyn Menares¹, Sebastián Cruz¹, Sofía Hidalgo¹, Eduardo Durán¹, César Oyarce¹, Alvaro Lladser¹*

¹Laboratory of Gene Immunotherapy, Fundación Ciencia & Vida, Santiago, Chile

^#These authors contributed equally to this work

*Corresponding author

Intradermal vaccination efficiently induces long-lasting antigen-specific cytotoxic CD8 T cell responses due to the abundance of highly specialized dendritic cells in the skin. However, the ability of intradermal vaccination to generate skin-resident memory CD8 T cells remains poorly characterized. Here we show that intradermal vaccination with a DNA vaccine encoding the model antigen ovalbumin generates OVA_(257-264)-specific CD8 T cell memory precursors (KLRG1-CD127+) expressing high levels of skin homing molecules E– and P–selectin ligands (ESL and PSL), as well as CXCR3. At the memory phase of the response, in addition to central- and effector-memory CD8 T cells found in lymphoid organs, antigen-specific memory CD8 T cells displaying a CD103+CD69+ phenotype accumulated in both vaccinated and non-vaccinated skin. Also, a population of antigen-specific CD103-CD69+ memory CD8 T cells was detected mainly in vaccinated skin. Intravascular staining allowed us to demonstrate that CD103+CD69+ CD8 T cells corresponded to truly resident memory T (T_RM) cells. This was further corroborated by in vivo depletion experiments using anti-CD8 monoclonal antibodies, which resulted in the elimination of CD8 T cells from lymphoid organs and blood, as well as CD103-CD69+ CD8 T cells from skin. Remarkably, antigen-specific CD8 T_RM cells were resistant to antibody-mediated in vivo depletion and completely suppressed the growth of intradermally injected ovalbumin-expressing B16F10 melanoma tumors. This work highlights the potential role of T_RM cells in antitumor immunity and the use of intradermal vaccination against malignancies and infections of the skin.

Funding acknowledgements

CONICYT PFB-16, CORFO-INNOVA 12IDL2-13348, CONICYT fellowship (to FGC, EL, SC).