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Role of tissue markers associated with tumor microenvironment in the progression and immune suppression of oral squamous cell carcinoma

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Abstract

Head and neck cancers (HNC) continues to dominate major cancers contributing to  mortality worldwide. Squamous cell carcinoma is the major type of HNC. Oral Squamous Cell Carcinoma grouped under HNC is a malignant tumor occurring in the oral cavity. The primary risk factors of OSCC are tobacco, alcohol consumption, etc. This review focuses on modulations, mechanisms, growth and differentiation of oral squamous cell carcinoma. Cancer cell surrounds itself with a group of elements forming a favorable environment known as tumor microenvironment (TME). It consists of numerous cells which includes immune cells, blood cells and acellular components that are responsible for the progression, immunosuppression, metastasis and angiogenesis of cancer. This review highlights the most important tissue biomarkers (mTOR, CAF, FOXp3, CD163, CD33, CD34) that are associated with TME cells. mTOR remains as the primary regulator responsible in cancer and its importance towards immune-suppression is highlighted. Tumor-associated macrophages associated with cancer development and its relationship with immunomodulatory mechanism and Tregs, which are potential blockers of immune response and its mechanism and aberrations are discussed. Cancer-associated fibroblasts that are a part of TME and their role in evading the immune response and myeloid derived suppressor cells that have slight control over the immune response and their mechanism in the tumor progression is further explained. These markers have been emphasised as therapeutic targets and are currently in different stages of clinical trials.

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Abbreviations

HNC:

Head and neck cancer

EGFR:

Epidermal growth factor receptor

VEGF:

Vascular endothelial growth factor

OSCC:

Oral squamous cell carcinoma

HPV:

Human papilloma virus

TME:

Tumor microenvironment

ECM:

Extracellular matrix

mTOR:

Mammalian target of rapamycin

mTORC1 & 2:

Mammalian target of rapamycin complex 1 & 2

MDSCs:

Myeloid-derived suppressor cells

HSC:

Hematopoietic stem cells

TAM:

Tumor-associated macrophages

FOXp3::

Forkhead Box p3

Tregs:

Regulatory T cells

CAF:

Cancer-associated fibroblasts

RTK:

Receptor tyrosine kinase

GPCR:

G-protein coupled receptor

PIP2 & 3:

Phosphatidylinositol P 2 & 3

AKT:

Protein kinase B

PTEN:

Phosphatase and tensin

Rheb:

RAS homolog enriched in brain

TSC1 & 2:

Tuberous sclerosis protein 1 & 2

RAPTOR:

Regulatory associated protein of mTOR

TH :

T helper cells

DC:

Dendritic cells

NK:

Natural killer cells

APC:

Antigen presenting cells

IL:

Interleukin

TGF-β:

Tumor growth factor-β

MAPK:

Mitogen activated protein kinase

PDL1:

Programmed death ligand-1

PKD 3:

Protein kinase D3

LLSCC:

Lower lip squamous cell carcinoma

CXCL12:

CXC motif chemokine ligand 12

myCAF:

Myofibroblasts CAF

iCAF:

Inflammatory CAF

apCAF:

Antigen presenting CAF

EMT:

Epithelial mesenchymal transition

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Acknowledgements

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Funding

No funding was received for this review.

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Authors and Affiliations

  1. Department of Oral Pathology, Sri Ramachandra Dental College and Hospital, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India

    Suganya Ramalingam, Sivaramakrishnan Shantha & Harikrishnan Thamizhchelvan

  2. Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India

    Susruthan Muralitharan

  3. Department of Periodontics, Department of Dental Sciences, Tamil Nadu Dr. M.G.R. Medical University, Guindy, Chennai, 600032, India

    Uma Sudhakar

  4. Department of Biomedical Sciences, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India

    Venkatachalam Deepa Parvathi

  5. Susrutha Diagnostics, Chennai, India

    Susruthan Muralitharan

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Ramalingam, S., Shantha, S., Muralitharan, S. et al. Role of tissue markers associated with tumor microenvironment in the progression and immune suppression of oral squamous cell carcinoma. Med Oncol 40, 303 (2023). https://doi.org/10.1007/s12032-023-02169-5

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