Baseline Peripheral Blood Leukocytosis Is Negatively Correlated With T-Cell Infiltration Predicting Worse Outcome in Colorectal Cancers

Abstract

We aimed to explore the prognostic value of blood leukocyte and to generate a predictive model to refine risk stratification for colorectal cancers. 6,558 patients with colorectal cancers were identified eligible respectively in Fudan University Shanghai Cancer Center (FUSCC) between May, 2008 and October, 2016. Then the entire set is divided into a training set and a testing set. The prognostic value of pretreatment white blood cell count and clinicopathologic parameters in the context of tumor-infiltrating lymphocytes (TIL) and neutrophils was investigated. Conventional leukocytosis (≥10,000/μl) was significantly associated with decreased overall survival (OS) and disease-free survival (DFS) (p < 0.05). In fact, moderately elevated leukocyte (≥7,500/μl) has also been identified as an independent prognostic factor for survivals in the training, testing, and entire sets, respectively. And leukocytosis correlated with advanced T-stage (p < 0.001), M-stage (p < 0.001), poor differentiation tumor (p = 0.023) and Glasgow prognostic score, even predicted for worse relapse postoperatively (p = 0.001) and resistance to chemotherapy. In addition, nomograms on OS and DFS were established according to leukocytosis and other significant factors, demonstrating a great prediction accuracy. Importantly, pretreatment leukocytosis had a significantly lower intra-tumor CD3+ and CD8+ TIL infiltration (p < 0.001 and p = 0.033), whereas low CD3+ and CD8+ TIL expression in tumor were associated with worse OS and DFS (p = 0.02 and p = 0.015). In conclusion, our study validates leukocytosis as an independent prognostic factor in colorectal cancers. Our data provide for the first-time vital insight on the correlation of peripheral pretreatment leukocytosis with the tumor-infiltrating cells contexture and might be relevant for future risk stratification.

Tumor infiltrating immune cells (TIICs) as a biomarker for prognosis benefits in patients with osteosarcoma

“…At present, several immune risk score models used to quantify the immune status and indicate the prognosis of patients have been proposed in colorectal cancer and breast cancer respectively. These immune risk score models was proposed based on the counts of two lymphocyte populations of tumor centers and invasion margins [ 45 , 46 ]. The immune risk score model can be used to identify patients with recurrent risk or benefit from corresponding adjuvant chemotherapy.…”

Impact of preoperative white blood cell count on long-term outcome in patients undergoing surgery for colorectal cancer: A retrospective observational study of Chinese patients

“…Some studies have demonstrated that peripheral blood leukocytosis and neutrophilia re ected cancerrelated in ammation and has been proposed as prognostic immunological biomarkers for various malignancies 11,21 . A study validated leukocytosis as an independent prognostic factor in CRC, which provided for the rst-time vital insight on the correlation of peripheral pretreatment leukocytosis with the tumor-in ltrating cells contexture and might be relevant for future risk strati cation 22 . A meta-analysis showed that preoperative leukocytosis was common and correlates with poor pathological and survival outcomes in endometrial carcinoma patients 23 .…”

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

“…CRC is an inflammation-related tumor characterized by the infiltration of heterogeneous immune cells into tumor microenvironment and peripheral hematological disorders (6), which create a complex microenvironment that allows for the development of tumors (7 ). During acute inflammation, white blood cells (WBCs) are considered the first line of defense against microbial infection, protecting the host from pathogens (8).…”

“…However, in the state of long-term activation, continuous production of growth factors and reactive oxygen species may lead to permanent genomic changes and hinder the recruitment of lymphocytes by interacting with the DNA of the proliferating epithelium. Moreover, leukocytosis inhibits the activation of CD8 + tumor infiltrating lymphocytes by upregulating programmed death protein 1 (PD-1) on T lymphocytes and myeloid cells (7,9). In malignant diseases, leukocytes and neutrophils can dilate locally and throughout the body, promoting anti-cancer treatment resistance and tumor progression through angiogenesis, invasion, and inhibitory factors (10).…”