Publication

Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade.

Journal Paper/Review - Jul 7, 2022

Units
PubMed
Doi
Contact

Citation
Gaissler A, Meldgaard T, Heeke C, Babaei S, Tvingsholm S, Bochem J, Spreuer J, Amaral T, Wagner N, Klein R, Meier F, Garbe C, Eigentler T, Pawelec G, Claassen M, Weide B, Hadrup S, Wistuba-Hamprecht K. Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade. Front Immunol 2022; 13:906352.
Type
Journal Paper/Review (English)
Journal
Front Immunol 2022; 13
Publication Date
Jul 7, 2022
Issn Electronic
1664-3224
Pages
906352
Brief description/objective

Immune checkpoint blockade (ICB) is standard-of-care for patients with metastatic melanoma. It may re-invigorate T cells recognizing tumors, and several tumor antigens have been identified as potential targets. However, little is known about the dynamics of tumor antigen-specific T cells in the circulation, which might provide valuable information on ICB responses in a minimally invasive manner. Here, we investigated individual signatures composed of up to 167 different melanoma-associated epitope (MAE)-specific CD8+ T cells in the blood of stage IV melanoma patients before and during anti-PD-1 treatment, using a peptide-loaded multimer-based high-throughput approach. Additionally, checkpoint receptor expression patterns on T cell subsets and frequencies of myeloid-derived suppressor cells and regulatory T cells were quantified by flow cytometry. Regression analysis using the MAE-specific CD8+ T cell populations was applied to identify those that correlated with overall survival (OS). The abundance of MAE-specific CD8+ T cell populations, as well as their dynamics under therapy, varied between patients. Those with a dominant increase of these T cell populations during PD-1 ICB had a longer OS and progression-free survival than those with decreasing or balanced signatures. Patients with a dominantly increased MAE-specific CD8+ T cell signature also exhibited an increase in TIM-3+ and LAG-3+ T cells. From these results, we created a model predicting improved/reduced OS by combining data on dynamics of the three most informative MAE-specific CD8+ T cell populations. Our results provide insights into the dynamics of circulating MAE-specific CD8+ T cell populations during ICB, and should contribute to a better understanding of biomarkers of response and anti-cancer mechanisms.