Hemozoin-induced immunomodulation and prostate carcinogenesis: mechanisms and implications

Hemozoin (Hz) is a crystalline by-product, which is produced when the Plasmodium species destroy haemoglobin, and it is commonly recognised that it leads to how our bodies respond to malaria. Although we understand pretty well its immunological actions in infectious diseases, recent research indicates that chronic exposure to Hz may actually cause cancer by sustaining inflammation and altering the immune system. In this review, we examines how the relationship between the hemozoin induced immune changes contribute to prostate cancer development arises. The presence of Hz within the macrophages and dendritic cells can modulate inflammatory signalling pathways, including NF-kB, MAPK, and STAT3, particularly in the context of co-stimulation with parasite or host-derived ligands, thereby sustaining low-grade inflammation over time. These processes can result in amplified cell growth, inhibition of cell death, and genomic instability, which are typical of cancer. In addition, while several in vitro studies have reported that the purified hemozoin elicits weak or no cytokines, it has accumulated Hz amplify responses to infections or Toll-like receptor ligands, consistent with a primarily agonistic role. Hz is seen to direct macrophages to a tumour-promoting M2, suppress cytotoxic T-cells, and increase the performance of regulatory T cells, all of which are detrimental to the immune response against tumours. The connections between Toll-like receptor (TLR) signalling, oxidative stress, and PI3K/Akt/mTOR are also investigated in relation to the possibility of encouraging tumour development in prostate conditions. Epidemiologically, malaria endemic regions also report an increase in prostate cancer incidence, though this ecological overlap is subject to major cofounding, it raises the hypothesis that repeated exposure to malaria and subsequently Hz might contribute to prostate cancer, which necessitates further studies. In addition, improved malaria control, demographic ageing, coinfections, and other factors are likely to obscure any direct association. A better comprehension of these relationships may present the possibility of novel diagnostic measures and specific interventions.