Journal article
Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive transfer with tumor-infiltrating lymphocytes in melanoma
T-Cells and Cancer, Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark1
Lund University2
Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark3
Department of Health Technology, Technical University of Denmark4
Copenhagen University Hospital Herlev and Gentofte5
Universidad Nacional de San Martin6
Danish Cancer Society7
University College London8
Immunoinformatics and Machine Learning, Bioinformatics, Department of Health Technology, Technical University of Denmark9
Bioinformatics, Department of Health Technology, Technical University of Denmark10
...and 0 moreBACKGROUND. Neoantigen-driven recognition and T cell-mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with Tumor-Infiltrating Lymphocytes (TILs). Yet, how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined.
METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes.
We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with in-creased survival, and that detection of engrafted CD8+ T cells in post-treatment (i.e. originating from the TIL infusion product) were unique to responders of TIL-ACT.
Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUTIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma, and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells.
Language: | English |
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Publisher: | American Society for Clinical Investigation |
Year: | 2022 |
Pages: | 1-16 |
ISSN: | 15588238 and 00219738 |
Types: | Journal article |
DOI: | 10.1172/JCI150535 |
ORCIDs: | Kristensen, Nikolaj Pagh , Borch, Annie , 0000-0003-4561-1211 , Munk, Kamilla K. , 0000-0002-1831-6746 , Bentzen, Amalie Kai , 0000-0001-5395-7509 , 0000-0001-9537-4045 , 0000-0002-3536-5523 , Nielsen, Morten , 0000-0001-6865-0147 , Holm, Jeppe Sejerø , Hadrup, Sine Reker and 0000-0002-9451-6037 |