Inflammaging in melanoma: Precision control for optimizing immune checkpoint inhibition

Area of Science:

• Oncology
• Immunology
• Dermatology

Background:

• Aging is a risk factor for melanoma, associated with chronic inflammation ('inflammaging').
• Inflammaging can lead to immune dysfunction and reduced efficacy of immune checkpoint inhibitors (ICIs).
• Understanding inflammaging's role in melanoma is crucial for improving immunotherapy outcomes.

Purpose of the Study:

• To review the role of key inflammaging-associated cytokines (IL-6, IL-1, TNF-α) in melanoma progression.
• To discuss their impact on responses to immune checkpoint inhibitors (ICIs).
• To explore strategies for modulating these cytokines to enhance immunotherapy.

Main Methods:

• Literature review focusing on inflammaging, melanoma, and ICIs.
• Analysis of the roles of interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-α).
• Evaluation of preclinical and clinical evidence for cytokine-targeted therapies.

Main Results:

• IL-6 is a key mediator linking inflammation to immune suppression and ICI toxicity; its blockade may improve ICI efficacy and tolerability.
• IL-1 signaling contributes to melanoma inflammation and immune dysregulation, but clinical data for IL-1 targeted strategies are limited.
• TNF-α has context-dependent roles, potentially mediating anti-tumor immunity or ICI resistance.

Conclusions:

• Selective modulation of pathological inflammaging, not broad immune suppression, may enhance the therapeutic index of ICIs.
• Targeting specific cytokine pathways (e.g., IL-6) is a promising strategy to optimize melanoma immunotherapy, especially in inflammaging contexts.