The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

Abstract

BackgroundTumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time.MethodsFifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) 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 double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences.ResultsApproximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm2) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm2) and stroma (approximately 34/mm2) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm2) and stroma (13/mm2) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma were positively associated with patient's survival time in a univariate analysis (P < 0.01 or 0.001). In a multivariate Cox proportional hazards analysis, the M1 macrophage density in the tumor islets was an independent predictor of patient's survival time.ConclusionsThe M1 macrophage density in the tumor islets is an independent predictor of survival time in NSCLC patients.

Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute‐on‐chronic liver failure

“…34 The respective LIP indices in the macrophage subsets, CD11b 1 CD163 1 and HLA-DR 1 CD163 1 , were significantly higher in patients with ACLF-MOF, as compared to other groups. The cell numbers were not significantly altered, suggesting a probable classical activation of macrophage in iron production, storage as LIP, and release in ACLF patients.…”

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

“…This may explain the inconsistency that macrophages in tumor islets are stronger predictors for survival in early-stage NSCLC, [20][21][22] whereas those in the …”

“…19 TAMs have since been shown to differentially correlate with survival of NSCLC patients according to their microanatomic localization. As such, although stromal TAMs are frequently negatively associated with patient survival, 20,21 tumor islet TAMs are consistently positively correlated with patient survival. 21,22 Nevertheless, the fact that the majority of TAMs localize in the tumor stroma 2 and express protumor M2 markers 20 still supports a protumor role of TAMs in most NSCLC patients, as observed in earlier studies.…”

“…As such, although stromal TAMs are frequently negatively associated with patient survival, 20,21 tumor islet TAMs are consistently positively correlated with patient survival. 21,22 Nevertheless, the fact that the majority of TAMs localize in the tumor stroma 2 and express protumor M2 markers 20 still supports a protumor role of TAMs in most NSCLC patients, as observed in earlier studies. 18,19 Furthermore, this is supported by a recent report from Ohtaki et al, 23 who demonstrated an association between CD204-positive stromal macrophages and poor outcomes, indicating the protumor effect of stromal macrophages.…”

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

“…20 Other studies also showed a positive relationship between M1 infiltration and survival. [36][37][38][39][40] Notably, HPV-induced vulvar carcinomas are known for their good overall prognosis and survival rate of approximately 80%. 41,42 In the current study, the increased presence of single CD141 cells, representative for M1 macrophages, was related to a decreased RFS but so was the number of all intraepithelial CD141 cells, comprising both M1 and M2 macrophages.…”