Skip to Main content Skip to Navigation
Journal articles

CD40L confers helper functions to human intra-melanoma class-I-restricted CD4 + CD8 + double positive T cells

Abstract : Although CD4 C CD8 C double positive (DP) T cells represent a small fraction of peripheral T lymphocytes in healthy human donors, their frequency is often increased under pathological conditions (in blood and targeted tissues). In solid cancers such as melanoma, we previously demonstrated an enrichment of tumor reactive CD4 low CD8 high ab DP T cells among tumor-infiltrating lymphocytes of unknown function. Similarly to their single positive (SP) CD8 C counterparts, intra-melanoma DP T cells recognized melanoma cell lines in an HLA-class-I restricted context. However, they presented a poor cytotoxic activity but a strong production of diverse Th1 and Th2 cytokines. The aim of this study was to clearly define the role of intra-melanoma CD4 low CD8 high ab DP T cells in the antitumor immune response. Based on a comparative transcriptome analysis between intra-melanoma SP CD4 C , SP CD8 C and DP autologous melanoma-infiltrating T-cell compartments, we evidenced an overexpression of the CD40L co-stimulatory molecule on activated DP T cells. We showed that, like SP CD4 C T cells, and through CD40L involvement, DP T cells are able to induce both proliferation and differentiation of B lymphocytes and maturation of functional DCs able to efficiently prime cytotoxic melanoma-specific CD8 T-cell responses. Taken together, these results highlight the helper potential of atypical DP T cells and their role in potentiating antitumor response.
Document type :
Journal articles
Complete list of metadatas

Cited literature [68 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01702809
Contributor : Elizabeth Bernardo <>
Submitted on : Wednesday, February 7, 2018 - 11:26:30 AM
Last modification on : Friday, June 19, 2020 - 3:08:52 AM
Long-term archiving on: : Tuesday, May 8, 2018 - 12:37:30 PM

File

CD40LEq32016.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Tiphaine Parrot, Romain Oger, Houssem Benlalam, Diane Raingeard de la Blétière, Nicolas Jouand, et al.. CD40L confers helper functions to human intra-melanoma class-I-restricted CD4 + CD8 + double positive T cells. OncoImmunology, Taylor & Francis, 2016, 5 (12), pp.e1250991 (eCollection 2016). ⟨10.1080/2162402X.2016.1250991⟩. ⟨inserm-01702809⟩

Share

Metrics

Record views

177

Files downloads

258