Data from CTG-Initiated Cryptic Peptide Translation Up- and Downstream of a Canonical ATG Start Codon Is Enhanced by TLR Stimulation and Induces Tumor Regression in Mice Article Swipe
Ziye Song
,
Youkyung Lim
,
Anneloes van Krimpen
,
Mitchell A.A. Geleijnse
,
Manon Messchendorp
,
Jane S.A. Voerman
,
Ling Li
,
Emma G.M. Tondeur
,
Gunja Mishra
,
Brett J. Hos
,
Dwin G.B. Grashof
,
Ralph Stadhouders
,
Harmen J.G. van de Werken
,
Peter D. Katsikis
,
Christopher Schliehe
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/2326-6066.c.7960495
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/2326-6066.c.7960495
Cytotoxic T lymphocytes screen cells for signs of infection and transformation by recognizing peptides displayed on MHC class I molecules. Next to canonical ATG-initiated open reading frames (ORF), noncanonical translation can result in synthesis of nonconventional or “cryptic” polypeptides. These can originate from translation initiation at noncanonical start codons, a process previously associated with inflammation and oncogenic transformation. Cryptic translation products are efficiently presented on MHC class I molecules and therefore increasingly recognized as potential targets for cancer immunotherapy. In this study, we studied the impact of localization of a CTG-initiated ORF relative to a canonical ATG start codon on cryptic expression after innate immune stimulation. We generated immortalized C57BL/6J mouse–derived bone marrow progenitor cells (HoxB8) expressing tandem minigene constructs, which encoded a CTG-driven chicken ovalbumin–derived SIINFEKL (S8L) epitope (CTG-S8L; H-2Kb restriced) either up- or downstream of a canonical ATG-initiated UTY-derived peptide WI9. The treatment of HoxB8-derived macrophages with Toll-like receptor agonists enhanced position-independent CTG-S8L translation, without affecting ATG-driven expression. Downstream CTG-S8L translation was driven by leaky scanning or ribosome re-initiation rather than read-through translation. Mouse AE17 mesothelioma and B16F10 melanoma cells expressing cryptic S8L either up- or downstream of a canonical ORF were efficiently killed by H-2Kb/S8L-restriced OT-I T cells in vitro, even though their antigen expression levels were extremely low. Mice implanted with tumors expressing cryptic S8L showed delayed tumor progression in vivo. In summary, our study contributes to the characterization of noncanonical start codon–driven cryptic antigen translation and highlights its potential for cancer immunotherapy.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1158/2326-6066.c.7960495
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412818522
All OpenAlex metadata
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- OpenAlex ID
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https://openalex.org/W4412818522Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/2326-6066.c.7960495Digital Object Identifier
- Title
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Data from CTG-Initiated Cryptic Peptide Translation Up- and Downstream of a Canonical ATG Start Codon Is Enhanced by TLR Stimulation and Induces Tumor Regression in MiceWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-08-01Full publication date if available
- Authors
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Ziye Song, Youkyung Lim, Anneloes van Krimpen, Mitchell A.A. Geleijnse, Manon Messchendorp, Jane S.A. Voerman, Ling Li, Emma G.M. Tondeur, Gunja Mishra, Brett J. Hos, Dwin G.B. Grashof, Ralph Stadhouders, Harmen J.G. van de Werken, Peter D. Katsikis, Christopher SchlieheList of authors in order
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https://doi.org/10.1158/2326-6066.c.7960495Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1158/2326-6066.c.7960495Direct OA link when available
- Concepts
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Downstream (manufacturing), Stimulation, Translation (biology), Start codon, Peptide, Chemistry, Tumor cells, Biology, Cell biology, Molecular biology, Cancer research, Genetics, Endocrinology, Messenger RNA, Biochemistry, Gene, Engineering, Operations managementTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.can | 30, 40 |
| abstract_inverted_index.for | 5, 76, 244 |
| abstract_inverted_index.its | 242 |
| abstract_inverted_index.our | 227 |
| abstract_inverted_index.the | 84, 231 |
| abstract_inverted_index.up- | 133, 186 |
| abstract_inverted_index.was | 163 |
| abstract_inverted_index.AE17 | 176 |
| abstract_inverted_index.Mice | 212 |
| abstract_inverted_index.Next | 20 |
| abstract_inverted_index.OT-I | 198 |
| abstract_inverted_index.WI9. | 142 |
| abstract_inverted_index.bone | 111 |
| abstract_inverted_index.even | 203 |
| abstract_inverted_index.from | 42 |
| abstract_inverted_index.low. | 211 |
| abstract_inverted_index.open | 24 |
| abstract_inverted_index.than | 172 |
| abstract_inverted_index.this | 80 |
| abstract_inverted_index.were | 193, 209 |
| abstract_inverted_index.with | 53, 148, 214 |
| abstract_inverted_index.(S8L) | 127 |
| abstract_inverted_index.Mouse | 175 |
| abstract_inverted_index.These | 39 |
| abstract_inverted_index.after | 102 |
| abstract_inverted_index.cells | 4, 114, 181, 200 |
| abstract_inverted_index.class | 17, 66 |
| abstract_inverted_index.codon | 98 |
| abstract_inverted_index.leaky | 166 |
| abstract_inverted_index.signs | 6 |
| abstract_inverted_index.start | 47, 97, 235 |
| abstract_inverted_index.study | 228 |
| abstract_inverted_index.their | 205 |
| abstract_inverted_index.tumor | 221 |
| abstract_inverted_index.which | 120 |
| abstract_inverted_index.(ORF), | 27 |
| abstract_inverted_index.B16F10 | 179 |
| abstract_inverted_index.cancer | 77, 245 |
| abstract_inverted_index.driven | 164 |
| abstract_inverted_index.either | 132, 185 |
| abstract_inverted_index.frames | 26 |
| abstract_inverted_index.immune | 104 |
| abstract_inverted_index.impact | 85 |
| abstract_inverted_index.innate | 103 |
| abstract_inverted_index.killed | 195 |
| abstract_inverted_index.levels | 208 |
| abstract_inverted_index.marrow | 112 |
| abstract_inverted_index.rather | 171 |
| abstract_inverted_index.result | 31 |
| abstract_inverted_index.screen | 3 |
| abstract_inverted_index.showed | 219 |
| abstract_inverted_index.study, | 81 |
| abstract_inverted_index.tandem | 117 |
| abstract_inverted_index.though | 204 |
| abstract_inverted_index.tumors | 215 |
| abstract_inverted_index.(HoxB8) | 115 |
| abstract_inverted_index.CTG-S8L | 154, 161 |
| abstract_inverted_index.Cryptic | 58 |
| abstract_inverted_index.antigen | 206, 238 |
| abstract_inverted_index.chicken | 124 |
| abstract_inverted_index.codons, | 48 |
| abstract_inverted_index.cryptic | 100, 183, 217, 237 |
| abstract_inverted_index.delayed | 220 |
| abstract_inverted_index.encoded | 121 |
| abstract_inverted_index.epitope | 128 |
| abstract_inverted_index.peptide | 141 |
| abstract_inverted_index.process | 50 |
| abstract_inverted_index.reading | 25 |
| abstract_inverted_index.studied | 83 |
| abstract_inverted_index.targets | 75 |
| abstract_inverted_index.without | 156 |
| abstract_inverted_index.C57BL/6J | 109 |
| abstract_inverted_index.SIINFEKL | 126 |
| abstract_inverted_index.agonists | 151 |
| abstract_inverted_index.enhanced | 152 |
| abstract_inverted_index.melanoma | 180 |
| abstract_inverted_index.minigene | 118 |
| abstract_inverted_index.peptides | 13 |
| abstract_inverted_index.products | 60 |
| abstract_inverted_index.receptor | 150 |
| abstract_inverted_index.relative | 92 |
| abstract_inverted_index.ribosome | 169 |
| abstract_inverted_index.scanning | 167 |
| abstract_inverted_index.summary, | 226 |
| abstract_inverted_index.(CTG-S8L; | 129 |
| abstract_inverted_index.Toll-like | 149 |
| abstract_inverted_index.affecting | 157 |
| abstract_inverted_index.canonical | 22, 95, 138, 191 |
| abstract_inverted_index.displayed | 14 |
| abstract_inverted_index.extremely | 210 |
| abstract_inverted_index.generated | 107 |
| abstract_inverted_index.implanted | 213 |
| abstract_inverted_index.infection | 8 |
| abstract_inverted_index.molecules | 68 |
| abstract_inverted_index.oncogenic | 56 |
| abstract_inverted_index.originate | 41 |
| abstract_inverted_index.potential | 74, 243 |
| abstract_inverted_index.presented | 63 |
| abstract_inverted_index.synthesis | 33 |
| abstract_inverted_index.therefore | 70 |
| abstract_inverted_index.treatment | 144 |
| abstract_inverted_index.ATG-driven | 158 |
| abstract_inverted_index.CTG-driven | 123 |
| abstract_inverted_index.Downstream | 160 |
| abstract_inverted_index.associated | 52 |
| abstract_inverted_index.downstream | 135, 188 |
| abstract_inverted_index.expressing | 116, 182, 216 |
| abstract_inverted_index.expression | 101, 207 |
| abstract_inverted_index.highlights | 241 |
| abstract_inverted_index.initiation | 44 |
| abstract_inverted_index.molecules. | 19 |
| abstract_inverted_index.previously | 51 |
| abstract_inverted_index.progenitor | 113 |
| abstract_inverted_index.recognized | 72 |
| abstract_inverted_index.restriced) | 131 |
| abstract_inverted_index.<i>in | 201, 223 |
| abstract_inverted_index.UTY-derived | 140 |
| abstract_inverted_index.constructs, | 119 |
| abstract_inverted_index.contributes | 229 |
| abstract_inverted_index.efficiently | 62, 194 |
| abstract_inverted_index.expression. | 159 |
| abstract_inverted_index.lymphocytes | 2 |
| abstract_inverted_index.macrophages | 147 |
| abstract_inverted_index.progression | 222 |
| abstract_inverted_index.recognizing | 12 |
| abstract_inverted_index.translation | 29, 43, 59, 162, 239 |
| abstract_inverted_index.immortalized | 108 |
| abstract_inverted_index.increasingly | 71 |
| abstract_inverted_index.inflammation | 54 |
| abstract_inverted_index.localization | 87 |
| abstract_inverted_index.mesothelioma | 177 |
| abstract_inverted_index.noncanonical | 28, 46, 234 |
| abstract_inverted_index.read-through | 173 |
| abstract_inverted_index.stimulation. | 105 |
| abstract_inverted_index.translation, | 155 |
| abstract_inverted_index.translation. | 174 |
| abstract_inverted_index.ATG-initiated | 23, 139 |
| abstract_inverted_index.CTG-initiated | 90 |
| abstract_inverted_index.HoxB8-derived | 146 |
| abstract_inverted_index.polypeptides. | 38 |
| abstract_inverted_index.re-initiation | 170 |
| abstract_inverted_index.“cryptic” | 37 |
| abstract_inverted_index.codon–driven | 236 |
| abstract_inverted_index.immunotherapy. | 78 |
| abstract_inverted_index.transformation | 10 |
| abstract_inverted_index.mouse–derived | 110 |
| abstract_inverted_index.nonconventional | 35 |
| abstract_inverted_index.transformation. | 57 |
| abstract_inverted_index.vivo</i>. | 224 |
| abstract_inverted_index.characterization | 232 |
| abstract_inverted_index.vitro</i>, | 202 |
| abstract_inverted_index.ovalbumin–derived | 125 |
| abstract_inverted_index.position-independent | 153 |
| abstract_inverted_index.H-2K<sup>b</sup> | 130 |
| abstract_inverted_index.immunotherapy.</p></div> | 246 |
| abstract_inverted_index.<div>Abstract<p>Cytotoxic | 0 |
| abstract_inverted_index.H-2K<sup>b</sup>/S8L-restriced | 197 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 15 |
| citation_normalized_percentile.value | 0.31427482 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |