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...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
11 December 2019
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| 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 
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| 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 |
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| 245 | 1 | 0 | |a Cancer neoepitopes for immunotherapy |b discordance between tumor-infiltrating T cell reactivity and tumor MHC peptidome display |c 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 |
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| 520 | |a 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. | ||
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| 650 | 4 | |a immune peptidome | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Mass Spectrometry | |
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| 650 | 4 | |a TIL (tumor infiltrating lymphocytes) | |
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