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Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review)

  • Authors:
    • Eliano Cascardi
    • Mario Della Mura
    • Nicoletta Sgarro
    • Silvia Minei
    • Gerardo Cazzato
    • Eugenio Maiorano
    • Lorenzo Lo Muzio
    • Maria Eleonora Bizzoca
    • Fábio França Vieira E Silva
    • Eleonora Lo Muzio
    • Mario Dioguardi
    • Andrea Ballini
  • View Affiliations / Copyright

    Affiliations: Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Section of Molecular Pathology, University of Bari, I-70121 Bari, Italy, Department of Biomedical Sciences and Human Oncology, Section of Oncology, University of Bari, I-70121 Bari, Italy, Department of Clinical and Experimental Medicine, University of Foggia, I-71122 Foggia, Italy, Department of Precision Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy, Department of Biomedical and Neuromotor Sciences, University of Bologna, I-40125 Bologna, Italy, Department of Life Science, Health and Health Professions, Link Campus University, I-00165 Rome, Italy
    Copyright: © Cascardi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 90
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    Published online on: February 9, 2026
       https://doi.org/10.3892/ijmm.2026.5761
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Abstract

The tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) represents a dynamic and heterogeneous ecosystem in which non-immune stromal cells play important roles in tumor progression, invasion and therapeutic resistance. Among these, cancer-associated fibroblasts (CAFs), derived mainly from normal oral fibroblasts under the influence of tumor-derived cytokines such as transforming growth factor β (TGF-β), angiopoietin-like 3 and platelet-derived growth factor-BB, are the most abundant. CAFs exhibit a myofibroblastic phenotype characterized by α-smooth muscle actin, fibroblast activation protein and integrin α6 expression and their presence correlates with aggressive tumor behavior and poor prognosis. Functionally, CAFs contribute to the ‘reverse Warburg effect’, remodeling of the extracellular matrix via matrix metalloproteinases and lysyl oxidase, promotion of angiogenesis and immunosuppression through cytokines such as TGF-β, interleukin (IL) 6 and IL-10. Programmed death-ligand 1 (PD-L1), a key immune checkpoint molecule, suppresses T-cell activation by binding programmed death-1 (PD-1) on lymphocytes while also exerting intrinsic oncogenic functions, including enhancement of epithelial-mesenchymal transition, proliferation and resistance to radiotherapy and chemotherapy. PD-L1-enriched extracellular vesicles released by CAFs and tumor cells further propagate immune evasion and metastasis. Although PD-1/PD-L1 blockade with pembrolizumab or nivolumab has improved outcomes in advanced OSCC, variability in PD-L1 expression and intratumoral heterogeneity challenge predictive accuracy. The present review integrated stromal and immune perspectives, emphasizing the dual oncogenic and immunomodulatory roles of CAFs and PD-L1 in shaping the OSCC TME and identifying future therapeutic opportunities targeting both compartments.
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Copy and paste a formatted citation
Spandidos Publications style
Cascardi E, Della Mura M, Sgarro N, Minei S, Cazzato G, Maiorano E, Lo Muzio L, Bizzoca ME, Vieira E Silva FF, Lo Muzio E, Lo Muzio E, et al: Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review). Int J Mol Med 57: 90, 2026.
APA
Cascardi, E., Della Mura, M., Sgarro, N., Minei, S., Cazzato, G., Maiorano, E. ... Ballini, A. (2026). Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review). International Journal of Molecular Medicine, 57, 90. https://doi.org/10.3892/ijmm.2026.5761
MLA
Cascardi, E., Della Mura, M., Sgarro, N., Minei, S., Cazzato, G., Maiorano, E., Lo Muzio, L., Bizzoca, M. E., Vieira E Silva, F. F., Lo Muzio, E., Dioguardi, M., Ballini, A."Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review)". International Journal of Molecular Medicine 57.4 (2026): 90.
Chicago
Cascardi, E., Della Mura, M., Sgarro, N., Minei, S., Cazzato, G., Maiorano, E., Lo Muzio, L., Bizzoca, M. E., Vieira E Silva, F. F., Lo Muzio, E., Dioguardi, M., Ballini, A."Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 90. https://doi.org/10.3892/ijmm.2026.5761
Copy and paste a formatted citation
x
Spandidos Publications style
Cascardi E, Della Mura M, Sgarro N, Minei S, Cazzato G, Maiorano E, Lo Muzio L, Bizzoca ME, Vieira E Silva FF, Lo Muzio E, Lo Muzio E, et al: Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review). Int J Mol Med 57: 90, 2026.
APA
Cascardi, E., Della Mura, M., Sgarro, N., Minei, S., Cazzato, G., Maiorano, E. ... Ballini, A. (2026). Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review). International Journal of Molecular Medicine, 57, 90. https://doi.org/10.3892/ijmm.2026.5761
MLA
Cascardi, E., Della Mura, M., Sgarro, N., Minei, S., Cazzato, G., Maiorano, E., Lo Muzio, L., Bizzoca, M. E., Vieira E Silva, F. F., Lo Muzio, E., Dioguardi, M., Ballini, A."Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review)". International Journal of Molecular Medicine 57.4 (2026): 90.
Chicago
Cascardi, E., Della Mura, M., Sgarro, N., Minei, S., Cazzato, G., Maiorano, E., Lo Muzio, L., Bizzoca, M. E., Vieira E Silva, F. F., Lo Muzio, E., Dioguardi, M., Ballini, A."Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 90. https://doi.org/10.3892/ijmm.2026.5761
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