Cancer neoepitopes for immunotherapy

• Verfasst von: Wickström, Stina L. [VerfasserIn]
• Verfasst von: Lövgren, Tanja [VerfasserIn]
• Verfasst von: Volkmar, Michael [VerfasserIn]
• Verfasst von: Reinhold, Bruce [VerfasserIn]
• Verfasst von: Duke-Cohan, Jonathan S. [VerfasserIn]
• Verfasst von: Hartmann, Laura [VerfasserIn]
• Verfasst von: Rebmann, Janina [VerfasserIn]
• Verfasst von: Mueller, Anja [VerfasserIn]
• Verfasst von: Melief, Jeroen [VerfasserIn]
• Verfasst von: Maas, Roeltje [VerfasserIn]
• Verfasst von: Ligtenberg, Maarten [VerfasserIn]
• Verfasst von: Hansson, Johan [VerfasserIn]
• Verfasst von: Offringa, Rienk [VerfasserIn]
• Verfasst von: Seliger, Barbara [VerfasserIn]
• Verfasst von: Poschke, Isabel [VerfasserIn]
• Verfasst von: Reinherz, Ellis L. [VerfasserIn]
• Verfasst von: Kiessling, Rolf [VerfasserIn]
• Titel: Cancer neoepitopes for immunotherapy
• Titelzusatz: discordance between tumor-infiltrating T cell reactivity and tumor MHC peptidome display
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: 11 December 2019
• Umfang: 15 S.
• Teil: volume:10
• Teil: year:2019
• Teil: extent:15
• Fussnoten: Gesehen am 24.01.2020
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2019
• Band/Heft Quelle: 10(2019) Artikel-Nummer 2766, 15 Seiten
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2019.02766
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: immune peptidome
• Sach-SW: Immunotherapy
• Sach-SW: Mass Spectrometry
• Sach-SW: neoepitopes
• Sach-SW: TIL (tumor infiltrating lymphocytes)
• K10plus-PPN: 1688494596

Abstract

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.