Buchumschlag

Cancer neoepitopes for immunotherapy: discordance between tumor-infiltrating T cell reactivity and tumor MHC peptidome display

Tumor-infiltrating lymphocytes (TIL) are considered enriched for T cells recognizing shared tumor-antigens or mutation-derived neoepitopes. We performed exome sequencing and HLA-A*02:01 epitope prediction from tumor cell lines from two HLA-A2 positive melanoma patients whose TIL displayed strong tum...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Wickström, Stina L. (VerfasserIn) , Lövgren, Tanja (VerfasserIn) , Volkmar, Michael (VerfasserIn) , Reinhold, Bruce (VerfasserIn) , Duke-Cohan, Jonathan S. (VerfasserIn) , Hartmann, Laura (VerfasserIn) , Rebmann, Janina (VerfasserIn) , Mueller, Anja (VerfasserIn) , Melief, Jeroen (VerfasserIn) , Maas, Roeltje (VerfasserIn) , Ligtenberg, Maarten (VerfasserIn) , Hansson, Johan (VerfasserIn) , Offringa, Rienk (VerfasserIn) , Seliger, Barbara (VerfasserIn) , Poschke, Isabel (VerfasserIn) , Reinherz, Ellis L. (VerfasserIn) , Kiessling, Rolf (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 11 December 2019
In: Frontiers in immunology
Year: 2019, Jahrgang: 10
ISSN:1664-3224
DOI:10.3389/fimmu.2019.02766
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2019.02766
Verlag: https://www.frontiersin.org/articles/10.3389/fimmu.2019.02766/full
Volltext
Verfasserangaben:Stina L. Wickström, Tanja Lövgren, Michael Volkmar, Bruce Reinhold, Jonathan S. Duke-Cohan, Laura Hartmann, Janina Rebmann, Anja Mueller, Jeroen Melief, Roeltje Maas, Maarten Ligtenberg, Johan Hansson, Rienk Offringa, Barbara Seliger, Isabel Poschke, Ellis L. Reinherz and Rolf Kiessling
Beschreibung
Zusammenfassung:Tumor-infiltrating lymphocytes (TIL) are considered enriched for T cells recognizing shared tumor-antigens or mutation-derived neoepitopes. We performed exome sequencing and HLA-A*02:01 epitope prediction from tumor cell lines from two HLA-A2 positive melanoma patients whose TIL displayed strong tumor reactivity. The potential neoepitopes were screened for recognition using autologous TIL by immunological assays and presentation on tumor major histocompatibility complex class I (MHC -I) molecules by Poisson detection mass spectrometry (MS). TIL from the patients recognized 5/181 and 3/49 of the predicted neoepitopes, respectively. MS-screening detected 3/181 neoepitopes on tumor MHC I from the first patient but only one was also among those recognized by TIL. Consequently, TIL enriched for neoepitope-specificity failed to recognize tumor cells, despite being activated by peptides. For the second patient, only after IFN-γ treatment of the tumor cells was one of 49 predicted neoepitopes detected by MS and this coincided with recognition by TIL sorted for the same specificity. Importantly, specific T cells could be expanded from patient and donor peripheral blood mononuclear cells (PBMC) for all neoepitopes recognized by TIL and/or detected on tumor MHC I. In summary, stimulating the appropriate inflammatory environment within tumors may promote neoepitope MHC-presentation while expanding T cells in blood may circumvent lack of specific TIL. The discordance in detection between physical and functional methods revealed here can be rationalized and used to improve neoantigen-targeted T cell immunotherapy.
Beschreibung:Gesehen am 24.01.2020
Beschreibung:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2019.02766

Ähnliche Einträge