Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach

Background: Adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and oral squamous cell carcinoma (OSCC) respond differently to immunotherapy. Pembrolizumab, an immune checkpoint inhibitor, has been approved by the Food and Drug Administration for the treatment of squamous cell carcinomas...

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Main Authors: Rajdeep Chakraborty, Charbel Darido, Aidan Tay, Thiri Zaw, Shoba Ranganathan, Fei Liu, Giuseppe Palmisano
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Oral Oncology Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772906024000062
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author Rajdeep Chakraborty
Charbel Darido
Aidan Tay
Thiri Zaw
Shoba Ranganathan
Fei Liu
Giuseppe Palmisano
author_facet Rajdeep Chakraborty
Charbel Darido
Aidan Tay
Thiri Zaw
Shoba Ranganathan
Fei Liu
Giuseppe Palmisano
author_sort Rajdeep Chakraborty
collection DOAJ
description Background: Adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and oral squamous cell carcinoma (OSCC) respond differently to immunotherapy. Pembrolizumab, an immune checkpoint inhibitor, has been approved by the Food and Drug Administration for the treatment of squamous cell carcinomas of the head and neck region. While MEC has shown some response to pembrolizumab; however, ACC is the least responsive. At the molecular level, head and neck cancers produce immunosuppressive molecules, resulting in immune evasion. Therefore, we hypothesised that salivary gland cancer cells produce a higher number of immunosuppressive proteins that cause suppression of the immune system's anti-tumour reactivity. Method: To determine differential protein expressions in OSCC, MEC, and ACC, we constructed cancer–immune cell co-culture models using different oral and salivary gland cancer cells. We performed SWATH, proteome profilers, gene ontology biological function, functional annotation clustering and protein interaction network analysis of all cancer samples in the co-culture models. Results: Analysis of the acquired data showed that the overexpressed proteins in the OSCC cells and participated more in metabolic process, while in the salivary gland cancer cells, overexpressed proteins participated more in immune processes, immune checkpoint pathway. Upon protein function analysis of salivary gland cells, the overexpressed proteins found negatively affecting immune process and checkpoint pathway proteins. Conclusion: Overall, we conclude that salivary gland cancer is less responsive to immunotherapy, possibly because of the high presence of immunosuppressive proteins. However, further analysis is needed to verify the biological functions and interactive partners of each differentially expressed protein in ACC cells.
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spelling doaj-art-7bdf0cdd78fb4d0595cdea57fc2f432e2025-01-09T06:15:10ZengElsevierOral Oncology Reports2772-90602024-03-019100160Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approachRajdeep Chakraborty0Charbel Darido1Aidan Tay2Thiri Zaw3Shoba Ranganathan4Fei Liu5Giuseppe Palmisano6Applied Biosciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; Corresponding author. Applied Biosciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia.Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, 3000, AustraliaApplied Biosciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; Australian e-Health Research Centre, Transformational Bioinformatics Group, CSIRO, New South Wales, AustraliaAustralian Proteome Analysis Facility, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, AustraliaApplied Biosciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, AustraliaSchool of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, AustraliaSchool of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; Australian Proteome Analysis Facility, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; GlycoProteomics Laboratory, Department of Parasitology, ICB, University of Sao Paulo, São Paulo, 05508-000, SP, BrazilBackground: Adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and oral squamous cell carcinoma (OSCC) respond differently to immunotherapy. Pembrolizumab, an immune checkpoint inhibitor, has been approved by the Food and Drug Administration for the treatment of squamous cell carcinomas of the head and neck region. While MEC has shown some response to pembrolizumab; however, ACC is the least responsive. At the molecular level, head and neck cancers produce immunosuppressive molecules, resulting in immune evasion. Therefore, we hypothesised that salivary gland cancer cells produce a higher number of immunosuppressive proteins that cause suppression of the immune system's anti-tumour reactivity. Method: To determine differential protein expressions in OSCC, MEC, and ACC, we constructed cancer–immune cell co-culture models using different oral and salivary gland cancer cells. We performed SWATH, proteome profilers, gene ontology biological function, functional annotation clustering and protein interaction network analysis of all cancer samples in the co-culture models. Results: Analysis of the acquired data showed that the overexpressed proteins in the OSCC cells and participated more in metabolic process, while in the salivary gland cancer cells, overexpressed proteins participated more in immune processes, immune checkpoint pathway. Upon protein function analysis of salivary gland cells, the overexpressed proteins found negatively affecting immune process and checkpoint pathway proteins. Conclusion: Overall, we conclude that salivary gland cancer is less responsive to immunotherapy, possibly because of the high presence of immunosuppressive proteins. However, further analysis is needed to verify the biological functions and interactive partners of each differentially expressed protein in ACC cells.http://www.sciencedirect.com/science/article/pii/S2772906024000062Adenoid cystic carcinomaMucoepidermoid carcinomaOral cancerOral squamous cell carcinomaImmunotherapyAnti-tumour reactivity
spellingShingle Rajdeep Chakraborty
Charbel Darido
Aidan Tay
Thiri Zaw
Shoba Ranganathan
Fei Liu
Giuseppe Palmisano
Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach
Oral Oncology Reports
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Oral cancer
Oral squamous cell carcinoma
Immunotherapy
Anti-tumour reactivity
title Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach
title_full Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach
title_fullStr Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach
title_full_unstemmed Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach
title_short Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach
title_sort inhibition of anti tumour reactivity of immune cells in the salivary gland cancer a proteomic approach
topic Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Oral cancer
Oral squamous cell carcinoma
Immunotherapy
Anti-tumour reactivity
url http://www.sciencedirect.com/science/article/pii/S2772906024000062
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