ArticleJournal for immunotherapy of cancer2022
In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
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- Integrative single-cell and bulk transcriptomic analyses identify DRAM1 as a candidate gene from fibroblast-associated transcriptional programs in colorectal cancer.Frontiers in oncology · 2026Article
- Changes in PD-1 expression on T lymphocyte subsets and related immune indicators before and after definitive chemoradiotherapy for esophageal squamous cell carcinoma.Annals of medicine · 2025Article
- Tumor cell-intrinsic PD-1 regulates chemotherapy resistance in colorectal cancer cells by activating downstream MAPK signaling.BJC reports · 2025Article
- A Novel Early Memory-Enriched Allogeneic NKG2D CAR-T Cell Therapy Based on CRISPR/Cas9 Technology for Solid Tumors.Cancers · 2025Article
- PD-1, PD-L1, and PD-L2 Expression as Predictive Markers in Rare Feline Mammary Tumors.Veterinary sciences · 2025Article
- Unveiling new therapeutic targets for esophageal cancer treatment through single-cell transcriptomics: pH-responsive nanobubbles enhance the efficacy of 125I radiotherapy.Journal of nanobiotechnology · 2025Article
- CXCL9 is a dual‑role biomarker in colorectal cancer linked to mitophagy and modulated by ALKBH5.Molecular medicine reports · 2025Article
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
- SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy.Molecular cancer · 2025Review
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- PTEN as a prognostic factor for radiotherapy plus immunotherapy response in nasopharyngeal carcinoma.Journal of nanobiotechnology · 2025Article
- Programmed cell death protein 1 in cancer cells.Cell communication and signaling : CCS · 2025Review
- Unveiling the dual role of circulating tumor cells in colorectal cancer immunotherapy: a comprehensive review of biomarker utility and immune microenvironment crosstalk.Frontiers in immunology · 2025Review
- Unlocking the mystery of the PD-1/PD-L1 axis: beyond the checkpoint hype.Frontiers in immunology · 2025Review
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) is one of the most prevalent and deadly tumors worldwide. The majority of CRC is resistant to anti-programmed cell death-1 (PD-1)-based cancer immunotherapy, with approximately 15% with high-microsatellite instability, high tumor mutation burden, and intratumoral lymphocytic infiltration. Programmed death-ligand 1 (PD-L1)/PD-1 signaling was described in solid tumor cells. In melanoma, liver, and thyroid cancer cells, intrinsic PD-1 signaling activates oncogenic functions, while in lung cancer cells, it has a tumor suppressor effect. Our work aimed to evaluate the effects of the anti-PD-1 nivolumab (NIVO) on CRC cells.
methodsIn vitro NIVO-treated human colon cancer cells (HT29, HCT116, and LoVo) were evaluated for cell growth, chemo/radiotherapeutic sensitivity, apoptosis, and spheroid growth. Total RNA-seq was assessed in 6-24 hours NIVO-treated human colon cancer cells HT29 and HCT116 as compared with NIVO-treated PES43 human melanoma cells. In vivo mice carrying HT29 xenograft were intraperitoneally treated with NIVO, OXA (oxaliplatin), and NIVO+OXA, and the tumors were characterized for growth, apoptosis, and pERK1/2/pP38. Forty-eight human primary colon cancers were evaluated for PD-1 expression through immunohistochemistry.
resultsIn PD-1+ human colon cancer cells, intrinsic PD-1 signaling significantly decreased proliferation and promoted apoptosis. On the contrary, NIVO promoted proliferation, reduced apoptosis, and protected PD-1+ cells from chemo/radiotherapy. Transcriptional profile of NIVO-treated HT29 and HCT116 human colon cancer cells revealed downregulation of BATF2, DRAM1, FXYD3, IFIT3, MT-TN, and TNFRSF11A, and upregulation of CLK1, DCAF13, DNAJC2, MTHFD1L, PRPF3, PSMD7, and SCFD1; the opposite regulation was described in NIVO-treated human melanoma PES43 cells. Differentially expressed genes (DEGs) were significantly enriched for interferon pathway, innate immune, cytokine-mediated signaling pathways. In vivo, NIVO promoted HT29 tumor growth, thus reducing OXA efficacy as revealed through significant Ki-67 increase, pERK1/2 and pP38 increase, and apoptotic cell reduction. Eleven out of 48 primary human colon cancer biopsies expressed PD-1 (22.9%). PD-1 expression is significantly associated with lower pT stage.
conclusionsIn PD-1+ human colon cancer cells, NIVO activates tumor survival pathways and could protect tumor cells from conventional therapies.
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