Expression of lymphocyte-activating gene 3 and T-cell immunoreceptor with immunoglobulin and ITIM domains in cutaneous melanoma and their correlation with programmed cell death 1 expression in tumor-infiltrating lymphocytes

淋巴细胞活化基因 3 和具有免疫球蛋白和 ITIM 结构域的 T 细胞免疫受体在皮肤黑色素瘤中的表达及其与肿瘤浸润淋巴细胞中程序性细胞死亡 1 表达的相关性

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作者:Woo Jin Lee, Ye Jin Lee, Myoung Eun Choi, Kyung A Yun, Chong Hyun Won, Mi Woo Lee, Jee Ho Choi, Sung Eun Chang

Background

Lymphocyte-activating gene 3 (LAG-3) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (TIGIT) domains are emerging checkpoint proteins.

Conclusion

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

Methods

Diagnostic tissue from 124 patients with melanoma were evaluated for LAG-3, TIGIT, and PD-1 expression by immunohistochemistry. Clinicopathologic features and survival were analyzed according to the expression of LAG-3, TIGIT, and PD-1.

Objective

We evaluated LAG-3 and TIGIT protein expression patterns, correlated these patterns with programmed cell death 1 (PD-1) protein expression, and determined their effects on clinicopathologic characteristics and biologic responses in melanoma.

Results

LAG-3 and TIGIT expression on tumor-infiltrating lymphocytes were significantly correlated with that of PD-1 and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of disease. However, PD-1 expression was not associated with clinicopathologic variables of prognostic significance. High expression of either LAG-3 or TIGIT was associated with worse survival. 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 of survival. Limitations: Retrospective study in a single institution and possibility of type 1 error.

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