{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T06:31:31Z","timestamp":1776148291709,"version":"3.50.1"},"reference-count":59,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"unspecified","delay-in-days":89,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["bmjonc"],"accepted":{"date-parts":[[2026,2,18]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Expression of CXC-chemokine receptor 4 (CXCR4) is associated with poor prognosis in colorectal cancer (CRC), metastasis and immune cell infiltration. Currently, only patients with metastatic CRC with mismatch repair deficient (dMMR) tumours (&lt;10%) are eligible for immune checkpoint blockade (ICB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      15 026 CRC tumour samples were analysed at Caris Life Sciences using whole-exome sequencing, whole-transcriptome sequencing and immunohistochemistry (IHC). This was a retrospective analysis in which all consecutive CRC cases between 2008 and 2023 with available molecular profiling and survival data were included. To elucidate the role of\n                      <jats:italic>CXCR4<\/jats:italic>\n                      mRNA expression in the tumour microenvironment (TME) and response to ICB, CRC samples were stratified by high and low quartiles of\n                      <jats:italic>CXCR4<\/jats:italic>\n                      mRNA expression levels and compared for molecular and clinical characteristics. Tumour mutational burden [TMB) and dMMR status were determined from DNA sequencing data. Immune cell infiltration was calculated from deconvolution of bulk RNA sequencing data. PD-L1 expression was determined by IHC stain intensity. Information for real-world survival and pembrolizumab treatment was obtained from the CODEai database using insurance claims-based data.\n                    <\/jats:p>\n                    <jats:p>Overall survival was calculated from date of either first specimen collection or treatment to last of healthcare contact with HR and p value calculated using the Cox proportional hazards model and log-rank test, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Metastatic sites showed higher\n                      <jats:italic>CXCR4<\/jats:italic>\n                      expression than primary tumours (22.7 vs 18.6 median transcripts per million [TPM], p&lt;0.001).\n                      <jats:italic>CXCR4<\/jats:italic>\n                      expression was lower in liver than non-liver metastases (21.2 vs 24.8 TPM, p&lt;0.001). Median\n                      <jats:italic>CXCR4<\/jats:italic>\n                      mRNA expression was positively associated with high TMB, dMMR and positive PD-L1 status. High\n                      <jats:italic>CXCR4<\/jats:italic>\n                      expression was associated with tumours with higher infiltration of B cells and M1\/M2 macrophages. High\n                      <jats:italic>CXCR4<\/jats:italic>\n                      expression in the primary tumour was associated with worse prognosis (HR 0.92, 95%\u2009CI 0.86 to 0.99, p&lt;0.02), regardless of dMMR status. In metastatic tumours, high\n                      <jats:italic>CXCR4<\/jats:italic>\n                      mRNA expression correlated with improved survival (HR 1.12, 95%\u2009CI 1.04 to 1.20, p=0.003). Remarkably, high\n                      <jats:italic>CXCR4<\/jats:italic>\n                      expression was associated with improved survival in all ICB-treated patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Correlation of high\n                      <jats:italic>CXCR4<\/jats:italic>\n                      expression with changes in the TME and improved outcomes following ICB suggests its potential for selecting immunotherapeutic strategies in CRC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjonc-2025-001003","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:25:25Z","timestamp":1774977925000},"page":"e001003","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["CXCR4 mRNA 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