Immunogenetic Signature of the MICA‐129 Val/Val Genotype Associated With Metastasis in Melanoma

MICA (major histocompatibility complex class I [MHC class I] chain‐related protein A) is a stress‐induced glycoprotein that functions as a ligand for the NKG2D (natural killer [NK] group 2 member D) receptor, expressed on NK cells and CD8 ⁺ T lymphocytes (cytotoxic T cells), playing a key role in tumor immune surveillance. In melanoma, modulation of this axis promotes tumor immune evasion. The functional MICA‐129 polymorphism (methionine [Met]/valine [Val]) alters the binding affinity to NKG2D, thereby influencing the cytotoxic immune response. This study included patients with basal cell carcinoma (BCC) and melanoma (primary and metastatic). The Functional Assessment of Cancer Therapy–Melanoma (FACT‐M) questionnaire was administered, followed by MICA‐129 genotyping using quantitative polymerase chain reaction (qPCR), measurement of soluble MICA (sMICA) by enzyme‐linked immunosorbent assay (ELISA), analysis of MICA and NKG2D expression on CD8 ⁺ T lymphocytes by flow cytometry, and assessment of inflammatory cytokines and angiogenic factors. A higher frequency of the Val/Val genotype was observed in metastatic melanoma, whereas serum sMICA levels did not differ among the groups. The Val variant was associated with reduced functional stability of the MICA–NKG2D axis, favoring tumor immune evasion. Primary melanoma exhibited a more pronounced inflammatory profile, whereas metastatic melanoma showed greater angiogenic activity, indicating a microenvironment conducive to tumor progression. These findings suggest that the MICA‐129 Val/Val genotype may serve as a prognostic biomarker and support the MICA–NKG2D axis as a potential therapeutic target in melanoma.