Eur J Immunol. 2019 Nov;49(11):2083-2094. doi: 10.1002/eji.201848039. Epub 2019 Aug 19.
Transcutaneous immunization with CD40 ligation boosts cytotoxic T lymphocyte mediated antitumor immunity independent of CD4 helper cells in mice.
Bialojan A1, Sohl J1, Rausch J1, Aranda Lopez P1, Denny M2, Langguth P2, Hartmann AK1,3, Yagita H4, Probst HC3, Schild H3, Radsak MP1.
1
Third Department of Medicine - Hematology, Oncology, Pneumology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
2
Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg-University, Mainz, Germany.
3
Institute of Immunology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
4
Department of Immunology, Juntendo University, Tokyo, Japan.
Transcutaneous immunization (TCI) is a novel vaccination strategy that utilizes skin-associated lymphatic tissue to induce immune responses. Employing T-cell epitopes and the TLR7 agonist imiquimod onto intact skin mounts strong primary, but limited memory CTL responses. To overcome this limitation, we developed a novel imiquimod-containing vaccination platform (IMI-Sol) rendering superior primary CD8+ and CD4+ T-cell responses. However, it has been unclear whether IMI-Sol per se is restricted in terms of memory formation and tumor protection. In our present work, we demonstrate that the combined administration of IMI-Sol and CD40 ligation unleashes fullblown specific T-cell responses in the priming and memory phase, strongly enhancing antitumor protection in mice. Interestingly, these effects were entirely CD4+ T cell independent, bypassing the necessity of helper T cells. Moreover, blockade of CD70 in vivo abrogated the boosting effect of CD40 ligation, indicating that the adjuvant effect of CD40 in TCI is mediated via CD70 on professional APCs. Furthermore, this work highlights the so far underappreciated importance of the CD70/CD27 interaction as a promising adjuvant target in TCI. Summing up, we demonstrate that the novel formulation IMI-Sol represents a powerful vaccination platform when applied in combination with sufficient adjuvant thereby overcoming current limitations of TCI. |
