Impact of RAS mutations on the immune infiltrate of colorectal liver metastases: A preliminary study

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Abstract

Kirsten rat sarcoma viral oncogene homolog KRAS proto-oncogene is the most common altered gene in colorectal cancer (CRC). Determining its mutational status, which is associated with worse prognosis and resistance to anti-epidermal growth factor receptor (EGFR) inhibitors, is essential for managing patients with CRC and colon liver metastases (CLM). Emerging studies highlighted the relationship of KRAS-mutated cancers and tumor microenvironment components, mainly with T cells. The aim of this study was to analyze the relationship of CLM immune cell infiltrate with KRAS mutational status. We performed a retrospective study on paraffin-embedded CLM tissue sections from patients surgically resected at the Department of Hepatobiliary and General Surgery of Humanitas Clinical and Cancer Center. We studied the distribution of lymphocytes (CD3+ cells), macrophages (CD163+), and neutrophils (CD66b+) in CLM tumoral and peritumoral area. Percentage of positive cells was correlated with tumor macroscopic characteristic, clinical aspects, and KRAS mutation. We observed a significant increase in CD66b+ cells in the peritumoral area in patients KRAS-mutated compared to KRAS wild-type patients. Percentages of lymphocytes and macrophages did not show significant differences. Further, neutrophils were found to be significantly increased also in the bloodstream of KRAS-mutated patients, indicating increased mobilization of neutrophils and recruitment in the CLM site. In conclusion, this study reveals a new intriguing aspect of the peritumoral microenvironment, which could pave the way for new prognostic and predictive markers for patient stratification.

Original languageEnglish
Pages (from-to)715-721
Number of pages7
JournalJournal of Leukocyte Biology
Volume108
Issue number2
DOIs
Publication statusPublished - Aug 2020

Keywords

  • Adult
  • Aged
  • Biomarkers
  • Biomarkers, Tumor
  • Colorectal Neoplasms/genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms/immunology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins p21(ras)/genetics
  • Tumor Microenvironment/genetics

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