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Cancer Neoepitopes ...
Cancer Neoepitopes for Immunotherapy : Discordance Between Tumor-Infiltrating T Cell Reactivity and Tumor MHC Peptidome Display
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- Wickstrom, Stina L. (författare)
- Karolinska Institutet,Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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- Lövgren, Tanja (författare)
- Karolinska Institutet,Uppsala universitet,Klinisk immunologi,Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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- Volkmar, Michael (författare)
- German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany
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- Reinhold, Bruce (författare)
- Dana Farber Canc Inst, Lab Immunobiol, Boston, MA USA;Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA
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- Duke-Cohan, Jonathan S. (författare)
- Dana Farber Canc Inst, Lab Immunobiol, Boston, MA USA;Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA
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- Hartmann, Laura (författare)
- Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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- Rebmann, Janina (författare)
- German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany
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- Mueller, Anja (författare)
- Martin Luther Univ Halle Wittenberg, Inst Med Immunol, Halle, Germany
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- Melief, Jeroen (författare)
- Karolinska Institutet,Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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- Maas, Roeltje (författare)
- Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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- Ligtenberg, Maarten (författare)
- Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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- Hansson, Johan (författare)
- Karolinska Institutet,Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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- Offringa, Rienk (författare)
- German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany
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- Seliger, Barbara (författare)
- Martin Luther Univ Halle Wittenberg, Inst Med Immunol, Halle, Germany
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- Poschke, Isabel (författare)
- German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany;German Canc Res Ctr, DKTK Immune Monitoring Unit, Heidelberg, Germany;Natl Ctr Tumor Dis NCT, Heidelberg, Germany
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- Reinherz, Ellis L. (författare)
- Dana Farber Canc Inst, Lab Immunobiol, Boston, MA USA;Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA
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- Kiessling, Rolf (författare)
- Karolinska Institutet,Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden
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(creator_code:org_t)
- 2019-12-11
- 2019
- Engelska.
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.frontier...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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-gamma 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Nyckelord
- TIL
- tumor
- Immune peptidome
- neoepitopes
- mass spectrometry
- immunotherapy
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Wickstrom, Stina ...
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Lövgren, Tanja
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Volkmar, Michael
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Reinhold, Bruce
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Duke-Cohan, Jona ...
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Hartmann, Laura
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Rebmann, Janina
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Mueller, Anja
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Melief, Jeroen
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Maas, Roeltje
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Ligtenberg, Maar ...
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Hansson, Johan
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Offringa, Rienk
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Seliger, Barbara
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Poschke, Isabel
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Reinherz, Ellis ...
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Kiessling, Rolf
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- MEDICIN OCH HÄLSOVETENSKAP
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NATURVETENSKAP
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Frontiers in Imm ...
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Uppsala universitet
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Karolinska Institutet