Ratio of Intratumoral Macrophage Phenotypes Is a Prognostic Factor in Epithelioid Malignant Pleural Mesothelioma

Abstract

HypothesisThe tumor micro-environment and especially the different macrophage phenotypes appear to be of great influence on the behavior of multiple tumor types. M1 skewed macrophages possess anti-tumoral capacities, while the M2 polarized macrophages have pro-tumoral capacities. We analyzed if the macrophage count and the M2 to total macrophage ratio is a discriminative marker for outcome after surgery in malignant pleural mesothelioma (MPM) and studied the prognostic value of these immunological cells.Methods8 MPM patients who received induction chemotherapy and surgical treatment were matched on age, sex, tumor histology, TNM stage and EORTC score with 8 patients who received chemotherapy only. CD8 positive T-cells and the total macrophage count, using the CD68 pan-macrophage marker, and CD163 positive M2 macrophage count were determined in tumor specimens prior to treatment.ResultsThe number of CD68 and CD163 cells was comparable between the surgery and the non-surgery group, and was not related to overall survival (OS) in both the surgery and non-surgery group. However, the CD163/CD68 ratio did correlate with OS in both in the total patient group (Pearson r −0.72, p<0.05). No correlation between the number of CD8 cells and prognosis was found.ConclusionsThe total number of macrophages in tumor tissue did not correlate with OS in both groups, however, the CD163/CD68 ratio correlates with OS in the total patient group. Our data revealed that the CD163/CD68 ratio is a potential prognostic marker in epithelioid mesothelioma patients independent of treatment but cannot be used as a predictive marker for outcome after surgery.

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…Up to date, this task has been accomplished using CD11c or NOS2 for M1 TAMs, and CD163, CD204, or CD206 for M2 TAMs. Indeed, increased M1 TAM densities seem to be associated with a favorable clinical outcome in NSCLC (Ma et al, 2010;Ohri et al, 2009), ovarian , colorectal (Edin et al, 2012), and gastric cancer (Zhang, Wang, et al, 2014a), while those of M2 are linked to poor prognosis in several tumors, including NSCLC (Hirayama et al, 2012;Ohtaki et al, 2010;Zeni et al, 2007), mesothelioma (Cornelissen et al, 2014), esophageal (Shigeoka et al, 2013), gastric cancer (Kawahara et al, 2010;Pantano et al, 2013), pancreatic (Hou et al, 2014;Ino et al, 2013;Kurahara et al, 2011;Sugimoto et al, 2014;Sugimura et al, 2015;Zeng et al, 2014), CRC (Herrera et al, 2013), HCC (Kong et al, 2013), Hodgkin lymphoma , renal (Dannenmann et al, 2013;Komohara et al, 2011;Xu et al, 2014), urothelial (Ichimura et al, 2014), breast (Medrek et al, 2012), endometrial (Kübler et al, 2014), ovarian (Lan et al, 2013), melanoma ( Jensen et al, 2009), and squamous oral carcinoma . Additionally, some studies have demonstrated that, when associated with poor clinical outcome, CD68 + cells are often correlated with the tumor microvessel density, in addition to HIF, VEGF (Chai et al, 2008), and matrix metalloproteinase expression (Bolat et al, 2006;Hanada et al, 2000;Leek et al, 1996;Osinsky et al, 2011;Valković et al, 2002), suggesting that they might have an ...…”

Physical and mechanical regulation of macrophage phenotype and function

“…For instance in cancer, M1 macrophages are known to have tumoricidal functions, whereas M2-like macrophages aid tumor cells in evading destruction from host immune cells, and promote angiogenesis, invasion and metastasis. The majority of tumor-associated macrophages adopt an M2-like phenotype, and their presence in tumors has been directly correlated with poor prognosis 13,14 . Contrarily in atherosclerosis, M1 macrophages are commonly viewed as atherogenic, while M2 macrophages are seen as atheroprotective.…”

Prostaglandin E2-mediated adenosinergic effects on CD14+cells: Self-amplifying immunosuppression in cancer

“…In mesothelioma, M2 macrophages with immunosuppressive features have been observed in the tumor; their ratio (CD163/ CD68) having a negative prognostic value. 20 The effect of sPE on skewing macrophage differentiation into M2 type has recently been demonstrated, 21,22 however, CD73 expression has not been studied on these cells.…”