Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma

BACKGROUNDNeoantigen-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.METHODSUsing 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.RESULTSWe 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 increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples 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.CONCLUSIONSThese 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.FUNDINGNEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:132

Enthalten in:

The Journal of clinical investigation - 132(2022), 2 vom: 18. Jan.

Sprache:

Englisch

Beteiligte Personen:

Kristensen, Nikolaj Pagh [VerfasserIn]
Heeke, Christina [VerfasserIn]
Tvingsholm, Siri A [VerfasserIn]
Borch, Annie [VerfasserIn]
Draghi, Arianna [VerfasserIn]
Crowther, Michael D [VerfasserIn]
Carri, Ibel [VerfasserIn]
Munk, Kamilla K [VerfasserIn]
Holm, Jeppe Sejerø [VerfasserIn]
Bjerregaard, Anne-Mette [VerfasserIn]
Bentzen, Amalie Kai [VerfasserIn]
Marquard, Andrea M [VerfasserIn]
Szallasi, Zoltan [VerfasserIn]
McGranahan, Nicholas [VerfasserIn]
Andersen, Rikke [VerfasserIn]
Nielsen, Morten [VerfasserIn]
Jönsson, Göran B [VerfasserIn]
Donia, Marco [VerfasserIn]
Svane, Inge Marie [VerfasserIn]
Hadrup, Sine Reker [VerfasserIn]

Links:

Volltext

Themen:

Antigens, Neoplasm
Cancer immunotherapy
Clinical Trial
Immunology
Journal Article
Melanoma
Multicenter Study
Research Support, Non-U.S. Gov't
T cells
Therapeutics

Anmerkungen:

Date Completed 17.02.2022

Date Revised 17.02.2022

published: Print

ClinicalTrials.gov: NCT00937625

Citation Status MEDLINE

doi:

10.1172/JCI150535

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM333507525