Dissecting the functions of cancer-associated fibroblasts to therapeutically target head and neck cancer microenvironment

Prieto-Fernández, Llara; Montoro-Jiménez, Irene; Luxán-Delgado, Beatriz de; Otero-Rosales, María; Rodrigo, Juan P.; Calvo, Fernando; García-Pedrero, Juana M.; Álvarez-Teijeiro, Saúl

doi:10.1016/j.biopha.2023.114502

Cited by 3 publications

(1 citation statement)

References 142 publications

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“…The remaining 10 % include lymphomas, adenocarcinomas, and sarcomas originating from lymphocytes, connective tissue cells, or salivary glands [7] . Globally, HNSCC stands as the sixth most prevalent cancer, with over 887,000 new cases annually and an estimated 450,000 deaths [8] . Its complex risk factors contributing to high morbidity and mortality involve long-term betel nut or tobacco chewing, local irritation, smoking, alcoholism, human tumor virus infections, etc.…”

Section: Introductionmentioning

confidence: 99%

Advanced progress of spatial metabolomics in head and neck cancer research

Zhao,

Shi,

Han

et al. 2024

Neoplasia

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Section: Introductionmentioning

confidence: 99%

Advanced progress of spatial metabolomics in head and neck cancer research

Zhao,

Shi,

Han

et al. 2024

Neoplasia

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Targeting oral tumor microenvironment for effective therapy

Budi

Farhood

2023

Cancer Cell Int

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Oral cancers are among the common head and neck malignancies. Different anticancer therapy modalities such as chemotherapy, immunotherapy, radiation therapy, and also targeted molecular therapy may be prescribed for targeting oral malignancies. Traditionally, it has been assumed that targeting malignant cells alone by anticancer modalities such as chemotherapy and radiotherapy suppresses tumor growth. In the last decade, a large number of experiments have confirmed the pivotal role of other cells and secreted molecules in the tumor microenvironment (TME) on tumor progression. Extracellular matrix and immunosuppressive cells such as tumor-associated macrophages, myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs) play key roles in the progression of tumors like oral cancers and resistance to therapy. On the other hand, infiltrated CD4 + and CD8 + T lymphocytes, and natural killer (NK) cells are key anti-tumor cells that suppress the proliferation of malignant cells. Modulation of extracellular matrix and immunosuppressive cells, and also stimulation of anticancer immunity have been suggested to treat oral malignancies more effectively. Furthermore, the administration of some adjuvants or combination therapy modalities may suppress oral malignancies more effectively. In this review, we discuss various interactions between oral cancer cells and TME. Furthermore, we also review the basic mechanisms within oral TME that may cause resistance to therapy. Potential targets and approaches for overcoming the resistance of oral cancers to various anticancer modalities will also be reviewed. The findings for targeting cells and potential therapeutic targets in clinical studies will also be reviewed.

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Tumor microenvironmental modification by the current target therapy for head and neck squamous cell carcinoma

Okuyama

Naruse

Yanamoto

2023

J Exp Clin Cancer Res

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Current clinical and observational evidence supports the EXTREME regimen as one of the standards of care for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) followed by the administration of immune checkpoint inhibitors (ICIs). In addition to the inhibition of the epidermal growth factor receptor (EGFR) pathway, cetuximab-mediated EGFR blockade has been shown to modulate tumor microenvironment (TME) characteristics, such as antibody-dependent cellular cytotoxicity (ADCC) activity, cytotoxic T-lymphocyte (CTL) infiltration into the tumor, anti-angiogenesis activity, and cytokine secretion via associated natural killer (NK) cells, etc.. On the other hand, there are reports that nivolumab affects the TME via Programmed cell death 1 (PD-1) inhibition, Interleukin-10 upregulation via T-cells, myeloid-derived suppressor cell-mediated immune escape induction, and tumor vessel perfusion by promoting CD8 + T-cell accumulation and Interferon-γ production in treatment-sensitive tumor cells. Actually, nivolumab administration can give T cells in the TME both immune superiority and inferiority. HNSCC treatment using cetuximab increases the frequency of FoxP3 + intratumoral effector regulatory T cells (Tregs) expressing CTL associated antigen (CTLA)-4, and targeting CTLA-4 + Tregs using ipilimumab restores the cytolytic function of NK cells, which mediate ADCC activity. Treg-mediated immune suppression also contributes to clinical response to cetuximab treatment, suggesting the possibility of the addition of ipilimumab or the use of other Treg ablation strategies to promote antitumor immunity. Moreover, also in hyper progression disease (HPD), intratumoral frequency of FoxP3 + effector Tregs expressing CTLA-4 is increased. Therefore, combination treatment with cetuximab plus anti-CTLA-4 antibody ipilimumab for HNSCC and this combination therapy after nivolumab administration for HPD may be expected to result in a higher tumor-control response. Based on the above evidence, we here suggest the efficacy of using these therapeutic strategies for patients with local-advanced, recurrent, and metastatic HNSCC and patients who do not respond well to nivolumab administration.

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Dissecting the functions of cancer-associated fibroblasts to therapeutically target head and neck cancer microenvironment

Cited by 3 publications

References 142 publications

Advanced progress of spatial metabolomics in head and neck cancer research

Advanced progress of spatial metabolomics in head and neck cancer research

Targeting oral tumor microenvironment for effective therapy

Tumor microenvironmental modification by the current target therapy for head and neck squamous cell carcinoma

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