Morphological heterogeneity of intratumoral macrophages in prostate tumors

Abstract

Background. Prostate cancer (PCa) is the most common human cancer worldwide. In the progression of prostate cancer, the total number of macrophages in the tumor tissue is associated with poor prognosis and increased risk of metastasis. However, the heterogeneity of intratumoral macrophages at various stages of PCa development, and the role of tumor-associated macrophages (TAMs) have been insuffciently investigated.The aim of the study was to analyze the morphological features, size and number of TAMs in PCa tissue samples, and to reveal their correlation with clinical data of patients.Material and Methods. Immunohistochemical analysis of 36 paraffn blocks of patients with PCa (pT2a–3bN0–1M0) was performed using antibodies to the scavenger receptor CD68.Results. Foamy CD68+ macrophages were found in the tumor tissue. The indicator “number of macrophages per total number of felds of view with macrophages” was the lowest in patients with a Gleason score of 6 (5.8) (11.0 – in patients with a Gleason score ≥ 8). Macrophages formed larger clusters in patients with severe PCa. Small but not large macrophages were signifcantly more common in patients with lymph node metastases (48 vs 24 in the N0 group; p=0.14). The number of small macrophages (smaller than 100 µm2) increased in a series of patients with Gleason scores of 6, 7 and ≥ 8 (24, 47.5, 72, respectively, p=0.052).Conclusion. As the tumor process progressed and the risk of biochemical recurrence increased, there was a trend towards an increase in the total area of large, foamy TAMs, presumably rich in lipids, as well as wider distribution of small macrophages with a tendency to form clusters. We hypothesize that foamy macrophages are involved in the further recruitment of small TAMs, subsequently leading to metastasis and tumor progression.

Prostate Cancer: Genetics, Epigenetics and the Need for Immunological Biomarkers

“…However, there are also cancer types, or specific intertumoral compartments, where levels of CD68+ TAMs in parenchyma in breast cancer have negative correlations with lymphatic metastasis, and in colorectal cancer, total CD68 levels positively correlate with overall survival and good prognosis [ 195 , 196 , 197 , 198 ]. Therefore, a number of studies have been performed focusing on specific TAM biomarkers, including scavenger/endocytic receptors, such as CD206, stabilin-1, MARCO, and others, which have demonstrated specific correlations with stages, metastasis and even therapy responses for lung, breast, colorectal, ovarian, prostate and other types of cancer [ 199 ].…”

“…Metabolic regulators, as identified for colorectal cancer, also show great potential [ 199 ]. In the case of prostate cancer, we have observed, even on the morphological level, two major phenotypes of TAMs: regular in size and shape, and large foamy-type TAMs [ 198 ]. Identification of the molecular profile and functions of these two major phenotypes of TAMs is needed to decipher their biomarker potential.…”

Macrophage diversity in human cancers: New insight provided by single-cell resolution and spatial context

“…Gene signature of LAMs can be a valuable criterion for cancer prognosis and prediction of the efficacy of anti-cancer therapy. Foamy lipid-laden macrophages were described before most extensively in atherosclerosis and tuberculosis, although they were also found in the following cancer types – NSCLC, ovarian, esophageal, CRC, prostate and gastric cancers [ 35 , 47 , [85] , [86] , [87] , [88] , [89] ]. One of the first studies showing abundant accumulation of foam-like TAMs in tumor tissue was the study of renal cancer [ 90 ].…”