Characterization of M1/M2 Tumour-Associated Macrophages (TAMs) and Th1/Th2 Cytokine Profiles in Patients with NSCLC

Abstract

Lung cancer is one of the most commonly reported cancers, and is known to be associated with a poor prognosis. The function of tumour-associated macrophages (TAMs) in lung cancer patients is multifaceted and the literature shows conflicting roles. (I) To analyze the Th1 and Th2 cytokine levels that contribute to the differentiation of M1 and M2 macrophage populations in the serum of patients with NSCLC versus non-cancer controls; and (II) To characterize the M1 and M2 macrophage populations within TAMs in different subtypes of NSCLC compared to non-tumour tissue. The Th1 and Th2 cytokine levels were analyzed in serum using the Bio-Plex assay. In addition, TAMs subsets from nontumour and tumour tissues were analyzed using immunohistochemistry (IHC). The level of IL-1β, IL-4, IL-6 and IL-8 was found to be increased in the serum of patients with large cell carcinoma but not in other NSCLC subtypes compared to non-cancer controls. In addition, the expression of CD68 and M2 marker CD163 was found to be increased (P≤0.0001) in all NSCLC subtypes compared to non-tumour tissues. In contrast, the expression of iNOS (M1 marker) was decreased in the tumour tissue of patients with adenocarcinoma (P≤0.01) and squamous carcinoma (P≤0.05) but not in large cell carcinoma compared to non-tumour tissue. The results of this study indicate that NSCLC might have the ability to alter phenotype within the lung tumour areas in the local environment (TAMs) but not in the bloodstream in the systemic environment (serum) except for large cell carcinoma.

In‐Depth Proteomic Analysis of Human Bronchoalveolar Lavage Fluid toward the Biomarker Discovery for Lung Cancers

“…Thus, many plasma proteins were detected in BALF, indicating that BALF is a great source of biomarkers for lung cancer. Indeed, these findings are in line with that of other studies published elsewhere (e.g., ANXA2) …”

“…This is probably because we combined the depletion with high pH RPLC fractionation. As shown in Figure , the numbers of identified BALF proteins in other studies were smaller than that of our study, ranging ≈800 to 1500 proteins . Next we compared our result with lung tumor proteome and human plasma proteome datasets .…”

High levels of CCL2 or CCL4 in the tumor microenvironment predict unfavorable survival in lung adenocarcinoma

“…The higher percentage of M2 TAMs in LUAD than LUSC tissues suggests that TAMs may tend to differentiate into the M2 subtype in the LUAD microenvironment, while most TAMs differentiate into the M1 subtype in LUSC. This differentiation may be responsible for the opposing roles of CCL2 or CCL4 for predicting prognosis in patients with LUAD and LUSC …”

The roles of microglia macrophages in tumor progression of brain cancer and metastatic disease

“…However, several studies showed that M1 cytokines (e.g., IFN-γ, TNF-α, IL-1β, IL-2, and IL-12) and their receptors were virtually absent in glioma, brain metastatic cell lines, and in human tissues whereas M2 immunosuppressive cytokine (i.e. IL-6, TGF-β) were greatly predominant in these cells (77, 85–87). Therefore, in brain tumor, the balance of upregulating M2 pro-tumor response and attenuated M1 anti-tumor immune response determine the promotion of tumor growth and invasion.…”