Stromal versus tumoral inflammation differentially contribute to metastasis and poor survival in laryngeal squamous cell carcinoma

Abstract

In solid tumors the biology and clinical course are strongly influenced by the interaction of tumor cells and infiltrating stromal host cells. The aim of this study was to assess the relative importance of stromal vs. tumoral inflammation for metastasis and survival in patients with laryngeal squamous cell carcinoma (LSCC).In 110 patients with tissues from histologically proven LSCC the expression of CD45, CD11b, CD3, MMP-9 and COX-2 was semiquantitatively analyzed in stromal regions and tumor nests.CD45, CD11b, CD3 and MMP-9 positive cells were more abundant in stroma whereas COX-2 was predominantly expressed in epithelial tumor nests. High expression of stromal CD45 and CD11b on immune cells in tumor regions correlated with COX-2 expression on tumor cells. High levels of CD45 in stroma as well as CD11b and COX-2 in tumor nests were associated with increased metastasis. In contrast, high frequencies of CD3 cells in the tumor core area were associated with reduced metastasis. Overall survival was reduced in patients with high stromal CD45, high tumoral CD11b and high tumoral COX-2 expression.This is the first study which separately analyzes peritumoral stroma and tumor core area in laryngeal squamous cell carcinoma in terms of CD45, CD11b, CD3, MMP-9 and COX-2 expression. Our results indicate that stroma and tumor islands need to be considered as two separate compartments in the inflammatory tumor microenvironment. Inflammatory stromal leukocytes, abundant myeloid cells in tumor regions and high expression of COX-2 on tumor cells are linked to metastatic disease and poor overall survival.

Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions

“…Most tumors consist of tumor cell islands and surrounding parenchyma or non-malignant stroma cells. Recently, we demonstrated a differential prognostic role of stromal vs. tumoral inflammation in head and neck squamous cell cancer (HNSCC) patients (57). Considering the emerging prognostic relevance of tumor-stroma constitution and sublocalization of immune infiltrates in solid tumors (58, 59), we especially focused on separate analyses of tumoral compartments in this study and could indeed find striking differences in TAN frequencies, motility and CXCR2-dependent regulation with regard to TAN localization.…”

Prognostic Impact of Tumor‐Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma Patients

“…12 Several studies have evaluated the prognostic role of TILs in LSCC. [13][14][15][16] However, most of these studies leave much to be desired: almost all patients received radiotherapy, which could influence the immune system of patients. To further explore the value of TILs and CD66b + neutrophils in LSCC prognostic evaluation, we evaluated the prevalence of CD3 + /CD4 + /CD8 + /Foxp3 + T-cells and CD66b + neutrophils that infiltrated LSCC, and their prognostic value in patients that received total or partial laryngectomy.…”

The Role of Cyclooxygenase-2 in Colorectal Cancer

“…Recent research suggests that PGE2 may indeed significantly promote development and progression of colorectal cancer [41,43,44]. COX-2 is also critical to promote metastasis [64] participating in metastasis to bone [65], brain [66], liver [67] and lymph nodes [68]. COX-2-medicated Factors like IL-11 is associated with cancer metastasis [65].…”