High preoperative white blood cell count determines poor prognosis and is associated with an immunosuppressive microenvironment in colorectal cancer

Meilin Weng; Wenling Zhao; Ying Yue; Miaomiao Guo; Ke Nan; Qingwu Liao; Minli Sun; Di Zhou; Changhong Miao

doi:10.3389/fonc.2022.943423

High preoperative white blood cell count determines poor prognosis and is associated with an immunosuppressive microenvironment in colorectal cancer

Front Oncol. 2022 Jul 29:12:943423. doi: 10.3389/fonc.2022.943423. eCollection 2022.

Authors

Meilin Weng^{1

2

3}, Wenling Zhao^{1

3}, Ying Yue^{1

3}, Miaomiao Guo^{1

3}, Ke Nan^{1

3}, Qingwu Liao^{1

3}, Minli Sun^{1

3}, Di Zhou^{1

3}, Changhong Miao^{1

3}

Affiliations

¹ Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, China.
³ Shanghai Key Laboratory of Perioperative Stress and Protection, Fudan University, Shanghai, China.

Abstract

Background: The correlation between high white blood cell (WBC) count and poor prognosis has been identified in various types of cancer; however, the clinical significance and immune context of WBC count in colorectal cancer remains unclear.

Methods: Between February 2009 and November 2014, 7,433 patients at the Shanghai Cancer Center who had undergone elective surgery for colorectal cancer were enrolled in this retrospective cohort study. Patients were divided into two groups: low and high preoperative WBC groups. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan-Meier method and Cox regression analysis were used to identify independent prognostic factors in colorectal cancer patients. Tumor-infiltrating immune cells in the high and low preoperative WBC groups were compared using immunohistochemical staining.

Results: Of the 7,433 patients who underwent colorectal cancer surgery and were available for analysis, 5,750 were included in the low preoperative WBC group, and 1,683 were included in the high preoperative WBC group. After propensity score matching, 1,553 patients were included in each group. Kaplan-Meier survival curves showed that a high preoperative WBC count was associated with a decreased overall survival (P = 0.002) and disease-free survival (P = 0.003), and that preoperative WBC count was an independent risk factor for overall survival (hazard ratio, 1.234; 95% confidence interval, 1.068-1.426; P = 0.004) and disease-free survival (hazard ratio, 1.210; 95% confidence interval, 1.047-1.397, P = 0.01). Compared to the low preoperative WBC group, the high preoperative WBC group exhibited higher expression of regulatory T cells (P = 0.0034), CD68⁺ macrophages (P = 0.0071), and CD66b⁺ neutrophils (P = 0.0041); increased expression of programmed cell death protein 1 (P = 0.005) and programmed cell death ligand 1 (P = 0.0019); and lower expression of CD8⁺ T cells (P = 0.0057) in colorectal cancer patients.

Conclusions: Our research indicates that a high preoperative WBC count is a prognostic indicator in colorectal cancer patients and is associated with an immunosuppressive tumor microenvironment, which could aid in future risk stratification.

Keywords: colorectal cancer; high preoperative WBC; long-term prognosis; preoperative leukocytosis; propensity score matching; tumor microenvironment.