Calming Down Immune Cells Could Hold Key to Melanoma Treatment

The gist: New research has shed light on why some patients’ melanoma tumors resist standard treatment. The scientists found that certain immune system cells produce chemical signals that may protect melanoma cells, and keep them from being destroyed. To get around this, the researchers say, drugs that affect the immune system (immunotherapy) could be combined with standard melanoma treatment. Indeed, such a combination is already being tested in a clinical trial—a research study with volunteer patients.

“Immune cells may be responsible for drug resistance in melanoma patients, according to research published in Cancer Discovery.”Cancer Research UK scientists at The University of Manchester found that chemical signals produced by a type of immune cell, called macrophages, also act as a survival signal for .

“When the researchers blocked the macrophages’ ability to make this signal – called TNF alpha – melanoma tumours were much smaller and easier to treat.

“When melanoma patients are given chemotherapy or radiotherapy it causes inflammation, increasing the number of macrophages in the body – and raising the levels of TNF alpha. This research suggests that targeting this chemical ‘survival signal’ could lead to new ways to treat the disease.”


Infiltrating Macrophages Promote Prostate Tumorigenesis via Modulating Androgen Receptor-Mediated CCL4–STAT3 Signaling

“Infiltrating macrophages are a key component of inflammation during tumorigenesis, but the direct evidence of such linkage remains unclear. We report here that persistent coculturing of immortalized prostate epithelial cells with macrophages, without adding any carcinogens, induces prostate tumorigenesis and that induction involves the alteration of signaling of macrophage androgen receptor (AR)-inflammatory chemokine CCL4–STAT3 activation as well as epithelial-to-mesenchymal transition and downregulation of p53/PTEN tumor suppressors. In vivo studies further showed that PTEN+/− mice lacking macrophage AR developed far fewer prostatic intraepithelial neoplasia (PIN) lesions, supporting an in vivo role for macrophage AR during prostate tumorigenesis. CCL4-neutralizing antibody effectively blocked macrophage-induced prostate tumorigenic signaling and targeting AR via an AR-degradation enhancer, ASC-J9, reduced CCL4 expression, and xenografted tumor growth in vivo. Importantly, CCL4 upregulation was associated with increased Snail expression and downregulation of p53/PTEN in high-grade PIN and prostate cancer. Together, our results identify the AR-CCL4-STAT3 axis as key regulators during prostate tumor initiation and highlight the important roles of infiltrating macrophages and inflammatory cytokines for the prostate tumorigenesis.”


Anti-CD47 Antibody–Mediated Phagocytosis of Cancer by Macrophages Primes an Effective Antitumor T-cell Response

“Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody–mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response.”


Anti-CD47 Antibody–Mediated Phagocytosis of Cancer by Macrophages Primes an Effective Antitumor T-cell Response

“Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody–mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response.”


Anti-CD47 Antibody–Mediated Phagocytosis of Cancer by Macrophages Primes an Effective Antitumor T-cell Response

“Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody–mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response.”