M2 macrophages and regulatory T cells in lethal prostate cancer

Abstract

Background Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (T regs ) can contribute to cancer progression by suppressing the anti‐tumor immune response. This study investigated the number of CD163‐positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and T regs . Methods This nested case‐control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163‐positive M2 macrophages and FOXP3/CD4‐positive T regs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and T regs were assessed using Spearman's rank‐order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts. Results The number of M2 macrophages and T regs showed a significant correlation ( P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23‐3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis. Conclusions Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as T regs , promote an immunosuppressive environment.

Prediction of Prognosis in Patients with Prostate Cancer by DNA Methylation Classification

“…For the cluster 3 group which has a poor prognosis, the proportion of memory B cells, M2 macrophages and Treg cells was signi cantly higher than that of cluster 1 and cluster 2. This is consistent with previous studies [16][17][18]. M2 macrophages and Treg cells are immunosuppressive cells that inhibit immune activation in tumors and promote the development of tumors.…”

“…Erlandsson et al [16] found that the higher the degree of tumor in ltration of M2 macrophages was, the greater the risk of death in patients with prostate cancer; the high degree of in ltration of M2 macrophages with a good prognosis and an enhanced response to chemotherapy [32]. WooJR et al [18] found that the degree of B lymphocyte in ltration in prostate cancer tissues was higher than that in adjacent tissues, and the degree of B lymphocyte in ltration in patients with a high risk of recurrence was higher than that in patients with a low risk of recurrence.…”

Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition

“…In the onco-immunity field, the role of tumor-associated macrophages, or TAMs, has recently gained great importance, since these can contribute to tumor progression, by promoting genetic instability and supporting metastasis. Furthermore, TAMs play a fundamental role in the response to cytoreductive therapy (chemotherapy and radiotherapy), where they can antagonize the antitumoral activity of these treatments [57,58]. Today, TAMs are considered sensitive therapeutic targets for immunomodulation of the tumor microenvironment.…”

Prostate Cancer

“…The Tregs, through their immunosuppressive effects, favor tumorpromoting characteristics; and the same has been demonstrated in PC patients, in whom elevated levels of Tregs conferred poor survival rates and a greater possibility of death. 38 Various immune populations are trafficked to the tumor site, and Treg trafficking is mainly mediated through the production of CCL17 and CCL22 by tumor-infiltrating T cells and TAMs through the CCL17/CCL22:CCR4 axis. 21…”

“…36 The CD163 marker (alias, the scavenger receptor that is more specific to the M2 macrophage) is indicative of poor prognosis in PC. 38 A growing body of evidence suggests that the chemokines secreted in the TME of PC by TAMs mediate activation of the CCL2:CCR2, CCL17:CCR4, and CCL22:CCR4 pathways, thereby promoting PC progression. 19 In the laboratory, Izumi et al 20 studied the role of TAMs in PC metastasis and demonstrated a role for the CCL2/CCR2-mediated STAT3 and the CCL17/ CCL22:CCR4 axis in PC progression.…”