LAG-3 & TIGIT Protein Expressions in Cutaneous Melanoma & Their Relationship with PD-1 Tumor-Infiltrating Lymphocytes

JAAD
15 Mar, 2019 ,

This was a retrospective study where they evaluated LAG-3 and TIGIT protein expression patterns and correlation with programmed death-1 (PD-1) expression and determined their effects on clinicopathological characteristics and biological responses in melanoma. Results suggest expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma.

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Background

Lymphocyte activating gene 3 (LAG-3) and T cell immunoglobulin and ITIM domain (TIGIT) are emerging checkpoint proteins.

Objective

We evaluated LAG-3 and TIGIT protein expression patterns and correlation with programmed death-1 (PD-1) expression and determined their effects on clinicopathological characteristics and biological responses in melanoma.

Methods

Diagnostic tissue from 124 cases of melanoma was evaluated by immunohistochemistry for LAG-3, TIGIT, and PD-1 expression. Clinicopathological features and survivals were analyzed according to the expression of LAG-3, TIGIT, and PD-1.

Results

LAG-3 and TIGIT expression on tumor-infiltrating lymphocytes was significantly correlated with that of PD-1 expression and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of the disease. However, PD-1 expression was not associated with clinicopathological variables, which are a prognostic index. High expression of either LAG-3 or TIGIT was associated with worse survivals. Subgroup analysis on the basis of Breslow thickness showed that both LAG-3 and TIGIT have prognostic significance regardless of tumor thickness. High expression of PD-1 was not predictive for survivals.

Limitations

A retrospective study in a single institution and the possibility of type 1 error.

Conclusion

Expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma.