The prognostic significance of VISTA and CD33-positive myeloid cells in cutaneous melanoma and their relationship with PD-1 expression

Jae Won Choi,Jee Ho Choi,Young Jae Kim,Mi Woo Lee,Chong Hyun Won,Woo Jin Lee,Kyung A Yun,Sung Eun Chang

doi:10.1038/s41598-020-71216-2

Jae Won Choi, Jee Ho Choi + Show 6 more

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https://doi.org/10.1038/s41598-020-71216-2

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V-domain Ig suppressor of T-cell activation (VISTA), which mediates immune evasion in cancer, is mainly expressed on hematopoietic cells and myeloid cells in the tumor. We evaluated correlations among the expression of VISTA, the myeloid-derived suppressor cell marker CD33, and programmed death-1 (PD-1), and determined their relationships with clinicopathological characteristics and disease outcomes in melanoma. Diagnostic tissue from 136 cases of melanoma was evaluated by immunohistochemistry for CD33, VISTA, and PD-1 expression. Dual immunofluorescence using CD33 and VISTA antibodies was performed. VISTA expression positively correlated with CD33 expression in melanoma tissue. Dual immunofluorescence staining revealed that VISTA was expressed by CD33-positive myeloid cells. PD-1 expression correlated with CD33 and VISTA expression. CD33 and VISTA expression were significantly associated with negative prognostic factors, including a deeper Breslow thickness and an advanced stage of disease. High expression of either CD33 or VISTA was associated with worse survival. Positivity for both VISTA and PD-1 predicted worse survival. Multivariate analysis showed that both CD33 and VISTA expression were independent prognostic factors in cutaneous melanoma. VISTA and CD33 expression are independent unfavourable prognostic factors in melanoma, which suggests their potential as therapeutic targets.

Highlights

V-domain Ig suppressor of T-cell activation (VISTA), which mediates immune evasion in cancer, is mainly expressed on hematopoietic cells and myeloid cells in the tumor
In oral squamous cell carcinoma, VISTA expression correlated with Myeloid-derived suppressor cells (MDSCs) markers (CD11b and CD33) and was associated with increased expression of IL13Rα2, an important cytokine involved in tumor metastasis and recruitment of MDSCs20
High CD33 expression was associated with a higher likelihood of lymph node (LN) involvement (P = 0.001) and an advanced American Joint Committee on Cancer (AJCC) stage (P = 0.005; Table 1)

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Introduction

V-domain Ig suppressor of T-cell activation (VISTA), which mediates immune evasion in cancer, is mainly expressed on hematopoietic cells and myeloid cells in the tumor. The prognostic significance of VISTA and its correlation with PD-1 expression has been evaluated in cutaneous m elanoma[21], the association between VISTA and CD33+ MDSCs has not been elucidated. We examined the expression of VISTA in primary melanoma tissue and analyzed its association with clinicopathological features and clinical outcome.

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