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

Abstract

Background: Tumor 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.

Methods: Ninety-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).

Results: The 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.

Conclusions: The 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.

Figure 1

Immunohistochemical detection of tumor-associated immune cells in non-small cell lung cancer tissues. (a) Macrophages (marker CD68) stained brown in the tumor islets (arrow) and tumor stroma (arrowhead). (b) Mature dendritic cells (marker CD83) stained brown in the tumor islets (arrow) and tumor stroma (arrowhead). (c) Cytotoxic T cells (marker CD8) stained brown in the tumor islets (arrow) and tumor stroma (arrowhead). Original magnification, × 400.

Figure 2

Kaplan-Meier survival curves demonstrate macrophage number or ratio in correlation to survival. [M] represents the macrophage number in the tumor islets and stroma (a), tumor islets (b), and tumor stroma (c). (d) The ratio of the macrophage number in the tumor islets "[M islets]" versus the macrophage number in the tumor stroma "[M stroma]".

Figure 3

Kaplan-Meier survival curves demonstrate mature dendritic cell number or ratio in correlation to survival. [D] represents the mature dendritic cell number in the tumor islets and stroma (a), tumor islets (b), and tumor stroma (c). (d) The ratio of the mature dendritic cell number in the tumor islets "[D islets]" versus the mature dendritic cell number in the tumor stroma "[D stroma]".

Figure 4

Kaplan-Meier survival curves demonstrate cytotoxic T cell number or ratio in correlation to survival. [T] represents the cytotoxic T cell number in the tumor islets and stroma (a), tumor islets (b), and tumor stroma (c). (d) The ratio of the cytotoxic T cell number in the tumor islets "[T islets]" versus the cytotoxic T cell number in the tumor stroma "[T stroma]".