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Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade
- Source :
- Gaißler, A, Meldgaard, T S, Heeke, C, Babaei, S, Tvingsholm, S A, Bochem, J, Spreuer, J, Amaral, T, Wagner, N B, Klein, R, Meier, F, Garbe, C, Eigentler, T K, Pawelec, G, Claassen, M, Weide, B, Hadrup, S R & Wistuba-Hamprecht, K 2022, ' Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade ', Frontiers in Immunology, vol. 13, 906352 . https://doi.org/10.3389/fimmu.2022.906352
- Publication Year :
- 2022
- Publisher :
- Frontiers Media SA, 2022.
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Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.dedup.wf.001..066172de6a61cf7224ba2a79d1f0c489
- Full Text :
- https://doi.org/10.3389/fimmu.2022.906352