The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

Abstract

BackgroundTumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time.MethodsNinety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0).ResultsThe numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patient's survival time.ConclusionsThe number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells.

Serum Kynurenic Acid: Possible Association with Invasiveness of Non-small Cell Lung Cancer

“…It has been previously shown that bronchial adenocarcinoma is characterized by aggressive development and poor prognosis compared to other histologic types of NSCLC (Cooke et al, 2010;Maeda et al, 2011;Tomaszek et al, 2011). This behavior may be attributed to the properties of the tumor itself, as well as to impaired anti-tumor immune response (Dai et al, 2010;Watanabe et al, 2011). Tryptofan degradation along the kynurenine pathway has been shown to be a major factor contributing to escape of tumor cells from immune surveillance (Munn et al, 1999).…”

“…Overall invasiveness of malignant tumors is dependent on the properties of the tumor at the molecular level (Watanabe et al, 2011), as well as on the proper response of the immune system (Dai et al, 2010 tumors, including lung cancer, may be attributed to metabolites of tryptophan degradation via kynurenine pathway (Munn and Mellor, 2007;Suzuki et al, 2010). It is the main pathway for tryptophan metabolism catalyzed by indoleamine 2,3-dioxygenase (IDO) and kynurenine aminotransferases (KATs), resulting in synthesis of kynurenic acid (KYNA) (Figure 1) (Fulop et al, 2007).…”

The Ratio of the Absolute Lymphocyte Count to the Absolute Monocyte Count Is Associated with Prognosis in Hodgkin's Lymphoma: Correlation with Tumor-Associated Macrophages

“…The aim of the present study was to examine the prognostic significance of the ALC/ AMC ratio at diagnosis and its relationship with TAMs in lesional tissues in patients with cHL, two parameters that reflect the tumor microenvironment and host immunity. Peripheral monocytosis has been associated with a poor prognosis in patients with lymphomas as well as those with solid tumors [21][22][23]. Myeloid-lineage cells may promote tumorigenesis through immunosuppression and the promotion of the tumor vasculature required for tumor growth and progression [24,25].…”

Advances in the prevention and treatment of lung cancer

“…108 Certain cell types in this infiltrate correlated with patient prognosis, including macrophages and lymphocytes, suggesting an important role in lung cancer pathogenesis. 109 In a syngeneic mouse model, lung cancer growth was reduced by restricting 'alternative' macrophage activation. 110 Research defining pathways that regulate lung cancer inflammation may reveal new targets for therapy.…”