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Peer-reviewedCC BY 4.0Frontiers in Immunology

IL18BP links antigen processing and presentation programs to a dendritic cell-enriched immunoregulatory state in colorectal cancer

  • Junyin Zheng1
  • Guodong Guo1
  • Yue Tian2
  • Liqi Chen1
  • Haoyun Xia1
  • Yiqing Jiang1
  • Dajia Lin1
  • Hao Zhang3
  • Nan Zhang4
  • Chenshen Huang1
4 affiliations
  1. 1Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University
  2. 2Fujian Medical University Union Hospital
  3. 3The Second Affiliated Hospital of Chongqing Medical University
  4. 4College of Life Science and Technology, Huazhong University of Science and Technology
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Abstract

Background: Antigen processing and presentation (APP) is required for tumor immune recognition, but its relationship with the immune landscape in colorectal cancer (CRC) remains incompletely defined. In this study, APP-related transcriptional programs were used as the starting point to identify immune-cell-associated biomarkers with prognostic and immunotherapeutic relevance in CRC.

Methods: Six public CRC bulk cohorts were analyzed to define APP-related molecular states. Weighted gene co-expression network analysis and four machine-learning frameworks, including Boruta, LassoLR, Pamr, and XGBoost, were applied to prioritize genes linked to APP activity. Single-cell analysis was performed with an atlas of 121 samples and 169,427 cells to identify the cellular origin of the candidate gene. Immune infiltration, cancer-immunity-cycle activity, immune checkpoint blockade (ICB) response, predicted drug response, somatic mutation patterns, and in vitro function were then evaluated.

Results: Two APP-associated patterns were identified and showed different survival outcomes and immune landscapes. Network- and machine-learning-based screening prioritized IL18BP as the main APP-associated candidate. Higher IL18BP expression was associated with longer survival and an immune-active phenotype, including stronger antigen-presentation signals, increased immune infiltration, checkpoint-related signatures, and cancer-immunity-cycle activation. Single-cell profiling showed that IL18BP was preferentially enriched in dendritic cells (DCs), linking the APP-derived bulk signature to a DC-centered immunoregulatory compartment. Across nine external ICB-treated cohorts, IL18BP showed response-classification performance. Drug-response prediction and somatic mutation analyses identified additional features associated with IL18BP-defined groups. In CRC cell lines, IL18BP knockdown increased proliferation, migration, and invasion.

Conclusion: These findings identify IL18BP as a DC-enriched, APP-associated biomarker in CRC. By connecting APP programs in bulk tumors with DC-level expression patterns at single-cell resolution, this study positions IL18BP as an APP-associated marker of a DC-enriched immune state. These findings support further evaluation of IL18BP for prognostic and immunotherapy stratification in colorectal cancer but do not establish a causal APP-DC-IL18BP pathway.

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Cite

BibTeXRIS
BibTeX
@article{zheng2026il18bp,
  title = {{IL18BP links antigen processing and presentation programs to a dendritic cell-enriched immunoregulatory state in colorectal cancer}},
  author = {Junyin Zheng and Guodong Guo and Yue Tian and Liqi Chen and Haoyun Xia and Yiqing Jiang and Dajia Lin and Hao Zhang and Nan Zhang and Chenshen Huang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1973858},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973858/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - IL18BP links antigen processing and presentation programs to a dendritic cell-enriched immunoregulatory state in colorectal cancer
AU  - Junyin Zheng
AU  - Guodong Guo
AU  - Yue Tian
AU  - Liqi Chen
AU  - Haoyun Xia
AU  - Yiqing Jiang
AU  - Dajia Lin
AU  - Hao Zhang
AU  - Nan Zhang
AU  - Chenshen Huang
PY  - 2026
DA  - 2026/10/05
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1973858
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973858/full
AB  - Background: Antigen processing and presentation (APP) is required for tumor immune recognition, but its relationship with the immune landscape in colorectal cancer (CRC) remains incompletely defined. In this study, APP-related transcriptional programs were used as the starting point to identify immune-cell-associated biomarkers with prognostic and immunotherapeutic relevance in CRC.  Methods: Six public CRC bulk cohorts were analyzed to define APP-related molecular states. Weighted gene co-expression network analysis and four machine-learning frameworks, including Boruta, LassoLR, Pamr, and XGBoost, were applied to prioritize genes linked to APP activity. Single-cell analysis was performed with an atlas of 121 samples and 169,427 cells to identify the cellular origin of the candidate gene. Immune infiltration, cancer-immunity-cycle activity, immune checkpoint blockade (ICB) response, predicted drug response, somatic mutation patterns, and in vitro function were then evaluated.  Results: Two APP-associated patterns were identified and showed different survival outcomes and immune landscapes. Network- and machine-learning-based screening prioritized IL18BP as the main APP-associated candidate. Higher IL18BP expression was associated with longer survival and an immune-active phenotype, including stronger antigen-presentation signals, increased immune infiltration, checkpoint-related signatures, and cancer-immunity-cycle activation. Single-cell profiling showed that IL18BP was preferentially enriched in dendritic cells (DCs), linking the APP-derived bulk signature to a DC-centered immunoregulatory compartment. Across nine external ICB-treated cohorts, IL18BP showed response-classification performance. Drug-response prediction and somatic mutation analyses identified additional features associated with IL18BP-defined groups. In CRC cell lines, IL18BP knockdown increased proliferation, migration, and invasion.  Conclusion: These findings identify IL18BP as a DC-enriched, APP-associated biomarker in CRC. By connecting APP programs in bulk tumors with DC-level expression patterns at single-cell resolution, this study positions IL18BP as an APP-associated marker of a DC-enriched immune state. These findings support further evaluation of IL18BP for prognostic and immunotherapy stratification in colorectal cancer but do not establish a causal APP-DC-IL18BP pathway.
SN  - 1664-3224
ER  -