Immunogenetic Signature of the MICA‐129 Val/Val Genotype Associated With Metastasis in Melanoma
4 affiliations
- 1Laboratory of Inflammation and Infectious Diseases Federal University of São Carlos (UFSCar) 13565–908 São Carlos SP Brazil ufscar.br
- 2Padre Albino University Centre – UNIFIPA 15809–144 Catanduva Brazil
- 3Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit School of Medicine São Paulo State University (UNESP) Botucatu 18618–687 Botucatu SP Brazil unesp.br
- 4Fiocruz Ribeirão Preto Oswaldo Cruz Foundation (Fiocruz) 14049–900 Ribeirão Preto SP Brazil fiocruz.br
Abstract
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.
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BibTeX
@article{fonseca2026immunogenetic,
title = {{Immunogenetic Signature of the MICA‐129 Val/Val Genotype Associated With Metastasis in Melanoma}},
author = {Bruna Somilio da Fonseca and Bruna D. L. Fragelli and Joice M. A. Rodolpho and Krissia F. Godoy and Camila F. B. Castro and Erick C. Casteli and Lucas R. Azevedo and Izabela A. Lopes and Luciana Benevides and Fernanda F. Anibal},
journal = {Journal of Immunology Research},
year = {2026},
month = nov,
doi = {10.1155/jimr/2883849},
url = {https://doi.org/10.1155/jimr/2883849},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immunogenetic Signature of the MICA‐129 Val/Val Genotype Associated With Metastasis in Melanoma
AU - Bruna Somilio da Fonseca
AU - Bruna D. L. Fragelli
AU - Joice M. A. Rodolpho
AU - Krissia F. Godoy
AU - Camila F. B. Castro
AU - Erick C. Casteli
AU - Lucas R. Azevedo
AU - Izabela A. Lopes
AU - Luciana Benevides
AU - Fernanda F. Anibal
PY - 2026
DA - 2026/11/01
JO - Journal of Immunology Research
DO - 10.1155/jimr/2883849
UR - https://doi.org/10.1155/jimr/2883849
AB - 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.
SN - 2314-8861
SN - 2314-7156
ER -