ArticleJournal for immunotherapy of cancer2020
Somatic POLE exonuclease domain mutations elicit enhanced intratumoral immune responses in stage II colorectal cancer.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan.Cell reports. Medicine · 2025Trial
- Co-Mutation of CREBBP/EP300 and POLE/POLD1 Identifies a TMB-High Subset of MSS CRC.International journal of molecular sciences · 2026Article
- Rarity within rarity: complete response to chemoimmunotherapy in a patient with polymerase epsilon (POLE)-mutated locally advanced jejunal carcinoma.The oncologist · 2026Article
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- ctDNA guided management of POLE mutant GI malignancies promotes exceptional responses and prolonged survival to immunotherapy.Frontiers in immunology · 2026Article
- Unveiling ctDNA Response: Immune Checkpoint Blockade Therapy in a Patient with POLE Mutation-Associated Early-Onset Colon Cancer.Current oncology (Toronto, Ont.) · 2025Article
- Sample size required for prognostic genes analysis in colorectal cancer.Discover oncology · 2025Article
- Review
- New insight in immunotherapy and combine therapy in colorectal cancer.Frontiers in cell and developmental biology · 2024Review
- Progress of Immune Checkpoint Inhibitors Therapy for pMMR/MSS Metastatic Colorectal Cancer.OncoTargets and therapy · 2024Review
- The game-changing impact ofFrontiers in oncology · 2024Review
- A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.Cancer medicine · 2024Article
- Review
- Immunotherapy and Targeted Therapy for Advanced Biliary Tract Cancer: Adding New Flavors to the Pizza.Cancers · 2023Review
- Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer.Cell reports. Medicine · 2023Article
- RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer.Frontiers in oncology · 2023Article
- Review
- High prevalence of unusual KRAS, NRAS, and BRAF mutations in POLE-hypermutated colorectal cancers.Molecular oncology · 2022Article
- POLE/POLD1 mutation and tumor immunotherapy.Journal of experimental & clinical cancer research : CR · 2022Review
- Pathological complete response to immune checkpoint inhibitor in patients with colorectal cancer liver metastases harboringJournal for immunotherapy of cancer · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies found patients with POLE exonuclease domain mutations (EDMs) in targeted exons were related to significant better outcomes in stage II-III colorectal cancer (CRC). The detailed mutational profile of the entire POLE exonuclease domain, tumor mutation burden (TMB) and immune cell infiltration in POLE EDMs tumors, and the prognostic value of such mutations in stage II CRCs were largely unknown to us. This study was to clarify the characteristics, immune response and prognostic value of somatic POLE EDMs in stage II CRC. A total of 295 patients with stage II CRC were sequenced by next-generation sequencing with a targeted genetic panel. Simultaneous detection of the immune cells was conducted using a five-color immunohistochemical multiplex technique. The detailed molecular characteristics, tumor-infiltrating lymphocyte (TIL) and prognostic effect of POLE EDMs in stage II CRC were analyzed. For stage II CRCs, the POLE EDMs were detected in 3.1% of patients. Patients with POLE EDMs were more prone to be microsatellite instability-high (MSI-H) (33.3% vs 11.2%, p=0.043), younger at diagnosis (median 46 years vs 62 years, p<0.001) and more common at right-sided location (66.7% vs 23.1%; p=0.003). All patients with POLE EMDs were assessed as extremely high TMB, with a mean TMB of 200.8. Compared with other stage II CRCs, POLE EDMs displayed an enhanced intratumoral cytotoxic T cell response, evidenced by increased numbers of CD8+TILs and CD8A expression. Patients with stage II CRCs could be classified into three risk subsets, with significant different 5 years disease-free survival rates of 100% for POLE EDMs, 82.0% for MSI-H and 63.0% for MSS, p=0.013. In conclusion, characterized by a robust intratumoral T cell response, ultramutated POLE EDMs could be detected in a small subset of stage II CRCs with extremely high TMB. Patients with POLE EDMs had excellent outcomes in stage II CRCs, regardless of MSI status. Sequencing of all the exonuclease domain of POLE gene is recommended in clinical practice.
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