The Ratio of CD86+/CD163+ Macrophages Predicts Postoperative Recurrence in Stage II-III Colorectal Cancer

Front Immunol. 2021 Aug 26:12:724429. doi: 10.3389/fimmu.2021.724429. eCollection 2021.

Abstract

Tumor-associated macrophages (TAMs) are pivotal for tumor progression and metastasis. We investigated the stromal CD86+TAM/CD163+TAM (CD86/CD163) ratio as a novel prognostic biomarker for stage II-III colorectal cancer (CRC). Two independently clinical cohorts of stage II-III CRC were retrospectively enrolled in this study. TAMs were detected using immunohistochemical staining for CD86 and CD163. The stromal CD86/CD163 ratio was calculated as a prognostic biomarker for recurrence-free survival (RFS) and overall survival (OS). Patients with a low CD86/CD163 ratio had shorter RFS (HR=0.193, p<0.001) and OS (HR=0.180, p<0.001) than patients with a high CD86/CD163 ratio in the training cohort. CD86/CD163 ratio may be an independent predictor for RFS (HR=0.233, p<0.001) and OS (HR=0.224, p<0.001) in the training cohort. We obtained equivalent results in the validation cohort. The CD86/CD163 ratio tends to have better predictive values than tumor stage in the training (AUC: 0.682 vs 0.654, p=0.538) and validation (AUC: 0.697 vs 0.659, p=0.586) cohorts. CD86/CD163 ratio effectively predicts RFS for stage II (HR=0.203, p<0.001) and stage III CRC (HR=0.302, p<0.001). CD86/CD163 ratio also effectively predicts RFS in CRC patients with adjutant chemotherapy (HR=0.258, p<0.001) and without adjutant chemotherapy (HR=0.205, p<0.001). The stromal CD86/CD163 ratio could be used for individual risk assessment of recurrence and mortality for stage II-III CRC. Together with tumor stage, this ratio will aid in the personal treatment.

Keywords: CD163; CD86; colorectal cancer; macrophage; ratio; recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • B7-2 Antigen / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Receptors, Cell Surface / metabolism*
  • Retrospective Studies
  • Risk Assessment

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-2 Antigen
  • CD163 antigen
  • Receptors, Cell Surface