Chronic Infections as Catalysts for Melanoma Aggressiveness: Insights into Tumour Microenvironment Modulation

Rocha, Layza Sá; Jacobowski, Ana Cristina; Reis, Eduarda Thiburcio Do Nascimento; Franco, Octávio Luiz; Cardoso, Marlon Henrique; Macedo, Maria Ligia Rodrigues

doi:10.31557/APJCP.2025.26.10.3531

Chronic Infections as Catalysts for Melanoma Aggressiveness: Insights into Tumour Microenvironment Modulation

Document Type : Systematic Review and Meta-analysis

Authors

¹ Laboratory of Protein Purification and their Biological Functions, Federal University of Mato Grosso do Sul, 79070-900 Campo Grande-MS, Brazil.

² Center for Proteomic and Biochemical Analysis, Postgraduate Program in Genomic Sciences and Biotechnology, Catholic University of Brasília, Brasília, Brazil.

³ S-Inova Biotech, Postgraduate Program in Biotechnology, Dom Bosco Catholic University, Campo Grande, Brazil.

10.31557/APJCP.2025.26.10.3531

Abstract

Background: Cutaneous melanoma is a highly aggressive skin cancer known for its metastatic potential and resistance to conventional therapies. While genetic and environmental factors are well-recognized in melanoma progression, the impact of chronic microbial infections is not fully understood. Recent studies suggest microbial pathogens interact with the tumour microenvironment, facilitating immune evasion, epithelial-mesenchymal transition (EMT), and therapy resistance. This study aims to explore how chronic infections contribute to melanoma aggressiveness and assess the potential of antimicrobial peptides (AMPs) as a new therapeutic approach. Methods: A systematic review was conducted according to PRISMA 2020 guidelines, utilising academic databases (PubMed, Scopus, Web of Science, and Google Scholar) from 2020 to 2025. Peer-reviewed studies were screened to identify microbial species linked to melanoma, antimicrobial resistance (AMR), and the effectiveness of AMPs. Data on cytokines, immune pathways, and bioinformatics approaches to AMP design were synthesized. Results: The review revealed that pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and Candida tropicalis exacerbate melanoma progression by inducing chronic inflammation, promoting pro-inflammatory cytokines (IL-6, TNF-α), and enhancing EMT, which aids tumour invasion and metastasis. AMR complicates treatment, particularly in immunocompromised patients. AMPs were identified as promising agents due to their dual action: antimicrobial activity and immunomodulation. Advances in bioinformatics and AI have facilitated the rational design of AMPs with improved specificity and reduced cytotoxicity, suggesting potential synergy with immune checkpoint inhibitors and targeted therapies. Conclusion: Chronic microbial infections significantly influence melanoma aggressiveness and treatment resistance. AMPs offer a promising, multifunctional therapeutic approach, addressing infection control and tumour microenvironment modulation. Combining AMPs with current immunotherapies may enhance melanoma management. Further research and clinical trials are needed to validate and optimise AMP-based treatments for personalised care.

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