Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells: a tumour-cell–based initiation of immune evasion

Rajdeep Chakraborty; Thiri Winn; Pallavi Khodlan; Charbel Darido; Giuseppe Palmisano; Arthur Chien; Aidan Tay; Shoba Ranganathan; Fei Liu

doi:10.1002/cnr2.70019

Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells: a tumour-cell–based initiation of immune evasion

Rajdeep Chakraborty^*, Thiri Winn, Pallavi Khodlan, Charbel Darido, Giuseppe Palmisano, Arthur Chien, Aidan Tay, Shoba Ranganathan, Fei Liu

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Introduction: Salivary gland adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC) occurs within the head and neck region. So far immune check point inhibitors failed in ACC. Gipie (CCDC88B) is a microtubule linker protein that activates immune cells. Gipie expressions found in head and neck cancer cells. We hypothesised that the presence of Gipie diminishes anti-tumour reactivity of immune cells towards head and neck cancer.

Method: To determine the effect of Gipie in oral and salivary gland cancer cells, Gipie was silenced in cancer cells in cancer-immune cells co-culture models and we performed 3D Z series confocal imaging, annexin V and immune activation flow cytometry, proteome profiler and discovery phase proteomics.

Results: ACC cells morphed into pseudonormal morphology in immune co-culture models. Silencing Gipie in ACC cells showed significant increase of apoptotic cells and activated natural killer cells, and lowering of regulatory T cells. Other salivary and oral cancer cells showed negligible effect of Gipie. Proteome profiler and proteomics assay confirmed Gipie affecting proliferation mechanism and immune activated proteins in ACC immune co-culture models.

Conclusion: Overall, we conclude that the presence of Gipie has a confounding role during the ACC–immune cell interaction.

Original language	English
Article number	e70019
Pages (from-to)	1-9
Number of pages	9
Journal	Cancer Reports
Volume	7
Issue number	9
Early online date	26 Sept 2024
DOIs	https://doi.org/10.1002/cnr2.70019
Publication status	Published - Sept 2024

Bibliographical note

Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Adenoid cystic carcinoma
Anti-tumour reactivity
Apoptosis
Cancer
Gipie
Head and neck cancer
Immunotherapy
Mucoepidermoid carcinoma
Oral cancer
Oral squamous cell carcinoma
head and neck cancer
apoptosis
oral squamous cell carcinoma
adenoid cystic carcinoma
immunotherapy
anti-tumour reactivity
cancer
mucoepidermoid carcinoma
oral cancer

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10.1002/cnr2.70019Licence: CC BY

Publisher version (open access)Final published version, 3.46 MBLicence: CC BY

Cite this

Chakraborty, R., Winn, T., Khodlan, P., Darido, C., Palmisano, G., Chien, A., Tay, A., Ranganathan, S., & Liu, F. (2024). Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells: a tumour-cell–based initiation of immune evasion. Cancer Reports, 7(9), 1-9. Article e70019. https://doi.org/10.1002/cnr2.70019

@article{80b5925b3ced49ab9c91daf254bb6961,

title = "Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells: a tumour-cell–based initiation of immune evasion",

abstract = "Introduction: Salivary gland adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC) occurs within the head and neck region. So far immune check point inhibitors failed in ACC. Gipie (CCDC88B) is a microtubule linker protein that activates immune cells. Gipie expressions found in head and neck cancer cells. We hypothesised that the presence of Gipie diminishes anti-tumour reactivity of immune cells towards head and neck cancer. Method: To determine the effect of Gipie in oral and salivary gland cancer cells, Gipie was silenced in cancer cells in cancer-immune cells co-culture models and we performed 3D Z series confocal imaging, annexin V and immune activation flow cytometry, proteome profiler and discovery phase proteomics. Results: ACC cells morphed into pseudonormal morphology in immune co-culture models. Silencing Gipie in ACC cells showed significant increase of apoptotic cells and activated natural killer cells, and lowering of regulatory T cells. Other salivary and oral cancer cells showed negligible effect of Gipie. Proteome profiler and proteomics assay confirmed Gipie affecting proliferation mechanism and immune activated proteins in ACC immune co-culture models. Conclusion: Overall, we conclude that the presence of Gipie has a confounding role during the ACC–immune cell interaction.",

keywords = "Adenoid cystic carcinoma, Anti-tumour reactivity, Apoptosis, Cancer, Gipie, Head and neck cancer, Immunotherapy, Mucoepidermoid carcinoma, Oral cancer, Oral squamous cell carcinoma, head and neck cancer, apoptosis, oral squamous cell carcinoma, adenoid cystic carcinoma, immunotherapy, anti-tumour reactivity, cancer, mucoepidermoid carcinoma, oral cancer",

author = "Rajdeep Chakraborty and Thiri Winn and Pallavi Khodlan and Charbel Darido and Giuseppe Palmisano and Arthur Chien and Aidan Tay and Shoba Ranganathan and Fei Liu",

note = "Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher. ",

year = "2024",

month = sep,

doi = "10.1002/cnr2.70019",

language = "English",

volume = "7",

pages = "1--9",

journal = "Cancer Reports",

issn = "2573-8348",

publisher = "Wiley-Blackwell, Wiley",

number = "9",

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Chakraborty, R , Winn, T, Khodlan, P, Darido, C, Palmisano, G, Chien, A , Tay, A , Ranganathan, S & Liu, F 2024, 'Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells: a tumour-cell–based initiation of immune evasion', Cancer Reports, vol. 7, no. 9, e70019, pp. 1-9. https://doi.org/10.1002/cnr2.70019

TY - JOUR

T1 - Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells

T2 - a tumour-cell–based initiation of immune evasion

AU - Chakraborty, Rajdeep

AU - Winn, Thiri

AU - Khodlan, Pallavi

AU - Darido, Charbel

AU - Palmisano, Giuseppe

AU - Chien, Arthur

AU - Tay, Aidan

AU - Ranganathan, Shoba

AU - Liu, Fei

N1 - Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2024/9

Y1 - 2024/9

N2 - Introduction: Salivary gland adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC) occurs within the head and neck region. So far immune check point inhibitors failed in ACC. Gipie (CCDC88B) is a microtubule linker protein that activates immune cells. Gipie expressions found in head and neck cancer cells. We hypothesised that the presence of Gipie diminishes anti-tumour reactivity of immune cells towards head and neck cancer. Method: To determine the effect of Gipie in oral and salivary gland cancer cells, Gipie was silenced in cancer cells in cancer-immune cells co-culture models and we performed 3D Z series confocal imaging, annexin V and immune activation flow cytometry, proteome profiler and discovery phase proteomics. Results: ACC cells morphed into pseudonormal morphology in immune co-culture models. Silencing Gipie in ACC cells showed significant increase of apoptotic cells and activated natural killer cells, and lowering of regulatory T cells. Other salivary and oral cancer cells showed negligible effect of Gipie. Proteome profiler and proteomics assay confirmed Gipie affecting proliferation mechanism and immune activated proteins in ACC immune co-culture models. Conclusion: Overall, we conclude that the presence of Gipie has a confounding role during the ACC–immune cell interaction.

AB - Introduction: Salivary gland adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC) occurs within the head and neck region. So far immune check point inhibitors failed in ACC. Gipie (CCDC88B) is a microtubule linker protein that activates immune cells. Gipie expressions found in head and neck cancer cells. We hypothesised that the presence of Gipie diminishes anti-tumour reactivity of immune cells towards head and neck cancer. Method: To determine the effect of Gipie in oral and salivary gland cancer cells, Gipie was silenced in cancer cells in cancer-immune cells co-culture models and we performed 3D Z series confocal imaging, annexin V and immune activation flow cytometry, proteome profiler and discovery phase proteomics. Results: ACC cells morphed into pseudonormal morphology in immune co-culture models. Silencing Gipie in ACC cells showed significant increase of apoptotic cells and activated natural killer cells, and lowering of regulatory T cells. Other salivary and oral cancer cells showed negligible effect of Gipie. Proteome profiler and proteomics assay confirmed Gipie affecting proliferation mechanism and immune activated proteins in ACC immune co-culture models. Conclusion: Overall, we conclude that the presence of Gipie has a confounding role during the ACC–immune cell interaction.

KW - Adenoid cystic carcinoma

KW - Anti-tumour reactivity

KW - Apoptosis

KW - Cancer

KW - Gipie

KW - Head and neck cancer

KW - Immunotherapy

KW - Mucoepidermoid carcinoma

KW - Oral cancer

KW - Oral squamous cell carcinoma

KW - head and neck cancer

KW - apoptosis

KW - oral squamous cell carcinoma

KW - adenoid cystic carcinoma

KW - immunotherapy

KW - anti-tumour reactivity

KW - cancer

KW - mucoepidermoid carcinoma

KW - oral cancer

UR - https://www.scopus.com/pages/publications/85205273938

U2 - 10.1002/cnr2.70019

DO - 10.1002/cnr2.70019

M3 - Article

C2 - 39324702

SN - 2573-8348

VL - 7

SP - 1

EP - 9

JO - Cancer Reports

JF - Cancer Reports

IS - 9

M1 - e70019

ER -

Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells: a tumour-cell–based initiation of immune evasion

Abstract

Bibliographical note

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A tumour-cell based initiation of immune evasion: developing 3D salivary gland cancer - immune coculture models

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Pseudonormal morphology of salivary gland adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells: a tumour-cell–based initiation of immune evasion

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Bibliographical note

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A tumour-cell based initiation of immune evasion: developing 3D salivary gland cancer - immune coculture models

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