Several Immune Checkpoint Regulators Are Associated With Poor Prognosis in Salivary Duct Carcinoma Patients

Salivary duct carcinoma (SDC) is an aggressive malignancy with limited treatment options, and immune checkpoint inhibitors may offer novel therapeutic alternatives.

The purpose of this study was to measure the association between immune checkpoint regulators and survival among patients with SDC.

This retrospective cohort study was performed at Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital and Fudan University Shanghai Cancer Center between April 2006 and November 2016. Subjects were SDC patients meeting the inclusion/exclusion criteria.

The predictor variable was the expression level of 5 immune checkpoint regulators (positive vs negative): programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin and mucin domain 3 (TIM-3).

The primary and secondary outcomes were disease-free survival (DFS) and overall survival.

The covariates were subjects' demographics, tumor characteristics, and androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status.

Survival analysis was performed using Kaplan-Meier curves and Cox regression models. Subtype comparisons were made using Pearson χ² or Fisher's exact test. Statistical analyses were performed using SPSS v.26. Statistical significance was P < .05.

The sample composed 54 subjects with a mean age of 59.39 years (SD 13.35) and 81% were male. PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, AR, and HER2 positivity rates were 37, 31, 33, 15, 44, 67, and 24%, respectively (P < .001). The DFS was worse in subjects positive for HER2, PD-1, PD-L1, or CTLA-4 (all P < .05), whereas positivity for LAG-3 or TIM-3 was not associated with DFS. Multivariate analysis identified PD-1/PD-L1 co-positivity as an independent negative prognostic factor for DFS (HR = 2.69, P = .02). HER2 positivity was also an independent predictor of poorer overall survival (P = .003). No significant differences in immune checkpoint regulator expression were observed across subtypes.

PD-1, PD-L1, CTLA-4, and HER2 positivity are associated with unfavorable clinical outcomes in SDC. Immune checkpoint regulator expression was comparable among AR/HER2 subtypes. PD-1, PD-L1, and CTLA-4 are potential therapeutic targets for SDC, particularly for the HER2/AR double-negative subtype.