The prognostic significance of carcinoma-associated fibroblasts and tumor-associated macrophages in nasopharyngeal carcinoma

Abstract

PurposeTumor stroma cells play an important role in the carcinogenesis and progression of cancer. The aim of the present investigation was to explore the predictive role of carcinoma-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) in nasopharyngeal carcinoma (NPC).Patients and methodsThe densities of CAFs and TAMs were measured by immunohistochemistry staining for α-smooth muscle actin (α-SMA), CD68, and CD163 in two sets of tissue microarrays including 260 pretreatment NPC tissues, that is, a training test comprising of 152 patients and a validation set comprising of 108 patients. Chi-square tests were performed for comparisons among the groups. Survival rates were estimated by using the Kaplan–Meier method and compared with log-rank tests. Cox proportional hazards models were used to identify significant independent variables.ResultsPatients older than 50 years showed a lower expression of CD68, and there was a positive relationship between the densities of CAFs and CD163+ TAMs (p=0.001). In the multivariate analysis of the training test, both α-SMA and CD163 were independent prognostic factors for overall survival and progression-free survival (all p<0.05). Based on the expression levels of α-SMA and CD163, patients were categorized into three groups: high-risk, intermediate-risk, and low-risk groups according to both high, either high, and both low, respectively. Survival analysis and Cox multivariate analysis showed that the risk groups based on α-SMA and CD163 expression were independent predictors for the survival of patients with NPC in the training test, which was also confirmed by the validation test.ConclusionA patient’s risk group based on the level of CD163+ TAMs and CAFs was an independent predictor of survival, which may facilitate patient counseling and individualized treatment.

High COX‐2 expression in cancer‐associated fibiroblasts contributes to poor survival and promotes migration and invasiveness in nasopharyngeal carcinoma

“…There are evidence suggesting that EBV‐infected NPC cells interacted with TME components to facilitate metastasis. An increased presence of Foxp3 + Treg cells and CD68 + tumor‐associated macrophages (TAMs) has been found in EBV‐positive NPC specimens and associated with poor prognosis . Another recent study has revealed an interacting loop between NPC cells and TAMs in driving NPC metastasis.…”

“…An increased presence of Foxp3 + Treg cells and CD68 + tumor-associated macrophages (TAMs) has been found in EBV-positive NPC specimens and associated with poor prognosis. 13 Another recent study has revealed an interacting loop between NPC cells and TAMs in driving NPC metastasis. In plethora of tumor microenvironmental cell types, cancer-associated fibroblasts (CAFs) have involved as one of the most promising targets owing to their abundant presence and functional significance in various tumor entities, including multiple myeloma, oral cancer, and gastric cancer.…”

Cancer-Associated Fibroblasts in Undifferentiated Nasopharyngeal Carcinoma: A Putative Role for the EBV-Encoded Oncoprotein, LMP1

“…In a similar vein, Yu et al (2018) also demonstrated the use of αSMA expression in CAFs, as well as CD163 expression on tumour-associated macrophages (TAMs), as independent predictors of survival in NPC prognostication using tissue microarrays [61]. To date, this is the only study linking CAFs and TAMs in NPC progression and survival, however studies in other cancers describe a crosstalk between resident CAFs and TAMs in the TME.…”

Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma

“…In HNSCC, macrophages promote cell migration, invasion and lymph node metastasis in in vitro and in vivo models, and are associated with worse outcome in patients (53,57,58). Moreover, studies show the correlation between the density of CAFs and TAMs with poor outcome in HNSCC (59,60). Furthermore, one study reported that protumorigenic macrophage polarization is promoted in HNSCC tumors with high lactic acid concentrations (61).…”