Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma

Oral squamous cell carcinomas (OSCC) remain a major healthcare burden in Asian countries. In Pakistan alone, it is the most common cancer in males and second only to breast cancer in females. Alarmingly, treatment options for OSCC remain limited. With this context, investigations made to explore the...

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Main Authors: Sofia Ali Syed, Muhammad Asif Qureshi, Saeed Khan, Rajesh Kumar, Iqbal A. Muhammad Khyani, Bilal Ahmed Khan, Jawad Safdar
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/2/1627
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author Sofia Ali Syed
Muhammad Asif Qureshi
Saeed Khan
Rajesh Kumar
Iqbal A. Muhammad Khyani
Bilal Ahmed Khan
Jawad Safdar
author_facet Sofia Ali Syed
Muhammad Asif Qureshi
Saeed Khan
Rajesh Kumar
Iqbal A. Muhammad Khyani
Bilal Ahmed Khan
Jawad Safdar
author_sort Sofia Ali Syed
collection DOAJ
description Oral squamous cell carcinomas (OSCC) remain a major healthcare burden in Asian countries. In Pakistan alone, it is the most common cancer in males and second only to breast cancer in females. Alarmingly, treatment options for OSCC remain limited. With this context, investigations made to explore the inflammatory <i>milieu</i> of OSCC become highly relevant, with the hope of practicing immunotherapeutic approaches to address this highly prevalent tumor. We investigated the newly identified innate lymphoid cells (ILCs) and associated cytokines in well-defined human oral squamous cell carcinoma (OSCC) as well as in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced murine model of OSCC using flow cytometry and quantitative real-time polymerase chain reaction (qPCR). We further went on to explore molecular circuitry involved in OSCC by developing a murine model of OSCC and using an α-Thy1 antibody to inhibit ILCs. Amongst the ILCs that we found in human OSCC, ILC3 (23%) was the most abundant, followed by ILC2 (17%) and ILC1 (1%). Mice were divided into four groups: DMBA (n = 33), DMBA+antibody (Ab) (n = 30), acetone (n = 5), and control (n = 5). In murine OSCC tissues, ILC1 and ILC3 were down-infiltrated, while ILC2 remained unchanged compared to controls. Interestingly, compared to the controls (DMBA group), mice treated with the α-Thy1 antibody showed fewer numbers of large tumors, and a larger percentage of these mice were tumor-free at this study’s end point. We present novel data on the differential expansion/downsizing of ILCs in OSCC, which provides a pivotal basis to dive deeper into molecular circuitry and the OSCC tumor niche to devise novel diagnostic, therapeutic, and prognostic strategies to prevent/treat oral cancers.
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spelling doaj.art-bce53219163640eeb634aec11989e6052023-11-30T22:43:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242162710.3390/ijms24021627Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell CarcinomaSofia Ali Syed0Muhammad Asif Qureshi1Saeed Khan2Rajesh Kumar3Iqbal A. Muhammad Khyani4Bilal Ahmed Khan5Jawad Safdar6Department of Oral Pathology, Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi 75300, Sindh, PakistanDepartment of Pathology, Dow International Medical College, Dow University of Health Sciences, Karachi 75300, Sindh, PakistanDepartment of Pathology, Dow International Medical College, Dow University of Health Sciences, Karachi 75300, Sindh, PakistanDepartment of Otorhinolaryngology, Head and Neck Surgery, Dow Medical College, Dow University of Health Sciences, Karachi 74200, Sindh, PakistanDepartment of ENT, Head and Neck Surgery, Shaheed Mohtarma Benazir Bhutto Medical College, Lyari General Hospital, Karachi 74200, Sindh, PakistanDepartment of Pathology, Dow International Medical College, Dow University of Health Sciences, Karachi 75300, Sindh, PakistanOral & Maxillofacial Surgery, Dow Dental College, Dow University of Health Sciences, Karachi 74200, Sindh, PakistanOral squamous cell carcinomas (OSCC) remain a major healthcare burden in Asian countries. In Pakistan alone, it is the most common cancer in males and second only to breast cancer in females. Alarmingly, treatment options for OSCC remain limited. With this context, investigations made to explore the inflammatory <i>milieu</i> of OSCC become highly relevant, with the hope of practicing immunotherapeutic approaches to address this highly prevalent tumor. We investigated the newly identified innate lymphoid cells (ILCs) and associated cytokines in well-defined human oral squamous cell carcinoma (OSCC) as well as in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced murine model of OSCC using flow cytometry and quantitative real-time polymerase chain reaction (qPCR). We further went on to explore molecular circuitry involved in OSCC by developing a murine model of OSCC and using an α-Thy1 antibody to inhibit ILCs. Amongst the ILCs that we found in human OSCC, ILC3 (23%) was the most abundant, followed by ILC2 (17%) and ILC1 (1%). Mice were divided into four groups: DMBA (n = 33), DMBA+antibody (Ab) (n = 30), acetone (n = 5), and control (n = 5). In murine OSCC tissues, ILC1 and ILC3 were down-infiltrated, while ILC2 remained unchanged compared to controls. Interestingly, compared to the controls (DMBA group), mice treated with the α-Thy1 antibody showed fewer numbers of large tumors, and a larger percentage of these mice were tumor-free at this study’s end point. We present novel data on the differential expansion/downsizing of ILCs in OSCC, which provides a pivotal basis to dive deeper into molecular circuitry and the OSCC tumor niche to devise novel diagnostic, therapeutic, and prognostic strategies to prevent/treat oral cancers.https://www.mdpi.com/1422-0067/24/2/1627cytokinehumaninnate lymphoid cellsmurineoral squamous cell carcinomatumor burden
spellingShingle Sofia Ali Syed
Muhammad Asif Qureshi
Saeed Khan
Rajesh Kumar
Iqbal A. Muhammad Khyani
Bilal Ahmed Khan
Jawad Safdar
Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma
International Journal of Molecular Sciences
cytokine
human
innate lymphoid cells
murine
oral squamous cell carcinoma
tumor burden
title Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma
title_full Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma
title_fullStr Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma
title_full_unstemmed Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma
title_short Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma
title_sort differential regulation of innate lymphoid cells in human and murine oral squamous cell carcinoma
topic cytokine
human
innate lymphoid cells
murine
oral squamous cell carcinoma
tumor burden
url https://www.mdpi.com/1422-0067/24/2/1627
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