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Article

Immune checkpoint inhibitors in POLE/POLD1 proofreading-deficient CRC: from molecular basis to clinical practice and future directions.

Immunotherapy - 1 Mar 2026

Jiang Lei, Yang Zhongxia, Liu Xiaojun

Abstract excerpt

Immune checkpoint inhibitors (ICIs) have fundamentally reshaped the therapeutic paradigm for metastatic colorectal cancer (mCRC). Beyond the established dMMR/MSI-H population, a molecularly distinct, hyper-immunogenic subset-governed by pathogenic aberrations in the exonuclease domains of POLE/POLD1-has emerged as a pivotal clinical entity. Characterized by an ultra-hypermutated phenotype, these tumors harbor a...

Topics

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Colorectal Neoplasms
DNA Polymerase II
DNA Polymerase III
Immune Checkpoint Inhibitors
Immunotherapy

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Poly-ADP-Ribose Binding Proteins

Tumor Microenvironment

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Identifiers

PMID: 42017297
DOI: 10.1080/1750743X.2026.2662823
PMCID: PMC13182957

Genes

POLD1
POLE

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 1 Sept 2026.

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