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Simultaneous Expression of PD-1 and PD-L1 in Peripheral and Central Immune Cells and Tumor Cells in the Benign and Malignant Salivary Gland Tumors Microenvironment

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Abstract

Background

To investigate the differential expression of PD-1 and PD-L1 in salivary gland tumors (SGTs, malignant and benign subtypes) and determine their association with the clinicopathological characterization of the patients.

Methods

The immunohistochemistry was used to examine PD-1 and PD-L1 expression in specimens from 83 patients with primary SGTs including salivary ductal carcinoma (SDC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC), mucoepidermoid carcinoma (MEC), warthin’s tumors (WT), poleomorphic adenoma (PA) and other subtypes.

Results

The expression of PD-1 in peripheral and central immune cells (ICs) of MEC, and peripheral ICs of ACC was significantly higher than those with AdCC (P = 0.02, P = 0.02, P = 0.03, respectively). Interestingly, the expression of PD-1 was also observed in peripheral and central malignant tumor cells (TCs), particularly in SDC and ACC. Despite no significant difference in PD-L1 expression of TCs among malignant subtypes, the peripheral and central ICs of ACC and MEC were revealed to express PDL-1 significantly more than those with AdCC (P < 0.05). WTs were rich in PD-1/PD-L1 expressing ICs. However, the tumor microenvironment of PA generally had low levels of PD-1/PD-L1 expression. In general, the expression of PD-1 in peripheral and central TCs was found to be significantly higher in malignant tumors than in benign ones (P = 0.002 and P = 0.003, respectively).

Conclusion

The simultaneous presentation of PD-1 and PD-L1 in TCs and ICs of SGTs, their significant association with disease severity as well as the positive correlation between these immune checkpoints may suggest the therapeutic potential of anti-PD-1 and anti-PDL-1 combinational immunotherapy for SGTs.

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Data Availability

The authors declare that data supporting the findings of this study are available within the article.

Code Availability

Antibody anti-PD-1 monoclonal antibody (CAT. NO. IHC001-100; GenomeMe Richmond, Canada); anti-PDL-1 monoclonal antibody (CAT. NO. IHC441-7; GenomeMe Richmond, Canada). Software IBM SPSS statistical software (version 21, SPSS Inc, USA), IBM SPSS Statistics (RRID: SCR_016479); Graph Pad Prism 6 software package (Inc; San Diego CA, USA, 2003), (RRID: SCR_002798).

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Acknowledgements

This project was conducted as the MD thesis of Sajjad Gerdabi, and was financially supported by grants from Shiraz University of Medical Sciences, Shiraz, Iran (Grant No: 22827), as well as Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran (ICR-100-500).

Funding

This study was supported by a Master’s thesis grant from Shiraz University of Medical Sciences (Grant number: 22827) as well as from Shiraz Institute for Cancer Research (Grant number: ICR-100–500).

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Author notes

  1. Mohammad Reza Haghshenas and Nasrollah Erfani have equally contributed to this work.

Authors and Affiliations

  1. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Sajjad Gerdabi & Nasrollah Erfani

  2. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Sajjad Gerdabi, Razie Kiani, Mohammad Reza Haghshenas & Nasrollah Erfani

  3. Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Asadian

  4. Department of Otolaryngology, Otolaryngology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Bijan Khademi

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  1. Sajjad Gerdabi
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Correspondence to Mohammad Reza Haghshenas or Nasrollah Erfani.

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Gerdabi, S., Asadian, F., Kiani, R. et al. Simultaneous Expression of PD-1 and PD-L1 in Peripheral and Central Immune Cells and Tumor Cells in the Benign and Malignant Salivary Gland Tumors Microenvironment. Head and Neck Pathol 17, 178–192 (2023). https://doi.org/10.1007/s12105-022-01486-x

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