Abstract
The treatment options for patients with advanced salivary gland cancers (SGCs) are limited. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, the response to ICI immunotherapy is largely driven by the immune cell signatures within the tumor tissue and the para-tumoral tissue compartments. To date, there are no data on the expression of programed cell death protein-1/programed cell death protein-ligand 1 (PD-1/PD-L1) in SGC, which may enable the implementation of ICI immunotherapy for this disease. Thus, we performed an immunohistochemical analysis of PD-1 and PD-L1 expression in tumor cells and tumor-infiltrating immune cells (TIICs) in the tumor center and periphery of 62 SGC patients. The tumor periphery showed significantly higher expression of PD-L1 in tumor cells than in TIICs. Moreover, peripheral TIICs had significantly higher PD-1 expression than peripheral tumor cells. PD-1-positive tumor cells were detected exclusively in the tumor center of high-grade tumors, and most importantly, the presence of lymph node (LN) metastases and primary tumor stage significantly correlated with the presence of PD-L1-positive tumor cells in the tumor periphery. The PD-1/PD-L1 molecular signatures in SGC are clustered predominantly in the tumor periphery, reflect disease severity, and may predict the response to ICI immunotherapy in SGC patients.
Highlights
We examined the expression of programmed cell death (PD)-L1 and PD-1 in tumor cells and tumor-infiltrating immune cells (TIICs) in the center and periphery of primary tumors from 62 SGC patients with 13 different histological subtypes
We initially found no significant difference in the expression of PD-1 or PD-ligand 1 (PD-L1) in tumor cells and TIICs in the tumor center (Figure 3A, left panels) or in the peripheral tumor cells (Figure 3A, right top panel)
We found that disease severity did not correlate with the expression of PD-L1 in TIICs in either the tumor periphery or tumor center (Supplementary Figure S1), nor were there correlations between the abundantly expressed PD-1 in the TIICs in the tumor center (Figure 4A–C) or even in the much more abundantly expressed PD-1 in the peripheral TIICs (Figure 4D–F)
Summary
Salivary gland cancers (SGCs) represent a rare group of neoplasms, accounting for less than 5% of head and neck cancers [1]. According to the World Health Organization (WHO) classification, more than 30 histological subtypes of salivary gland tumors have been identified, and 24 of them are proposed as malignant [2]. Due to the rarity of these cancers and their extreme histological diversity, defining the optimal molecular targets for SGC treatment is extremely challenging [3]. Whereas early stages of SGC can be effectively treated by surgery, patients with unresectable, recurrent, and metastatic (advanced)
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