Microenvironment in Oral Potentially Malignant Disorders: Multi-Dimensional Characteristics and Mechanisms of Carcinogenesis

Deng, Shuzhi; Wang, Shimeng; Shi, Xueke; Zhou, Hongmei

doi:10.3390/ijms23168940

Cited by 10 publications

(9 citation statements)

References 128 publications

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“…One of the hallmarks of cancer is the abnormal regulation of cellular metabolism, which reconstitutes the TMME [ 14 , 33 ]. Cancer and stromal cells in a tumor adapt their anabolism and catabolism of glucose, lipid, and amino acid to sustain the energy and macromolecules needed for cancer growth [ 34 ].…”

Section: Characteristics Of the Tumor Metabolic Microenvironmentmentioning

confidence: 99%

TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

et al. 2022

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Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-β signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an “engine” of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-β signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-β ligands act as an “endocrine” cytokine and influence host metabolism. Therefore, having insight into the role of TGF-β signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-β to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-β-dependent mechanism reprogramming, paving the way for TGF-β-related antitumor therapy from the perspective of metabolism.

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Section: Characteristics Of the Tumor Metabolic Microenvironmentmentioning

confidence: 99%

TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

et al. 2022

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“…During carcinogenesis, the immune cells undergo reprogramming, which is also accompanied by the remodelling of the tumour microenvironment (TME) to avoid anti-cancer immune mechanisms. Furthermore, the changes in the tumour milieu impede and even inhibit the humoral and cellular immune responses and change potentially malignant anti-immune behaviours, e.g., by creating tumour escape mechanisms from immune surveillance [ 33 , 34 ]. Moreover, a number of extensive carcinogenic interactions can be identified between immunocompetent cells and the TME compounds and neoplastic cells.…”

Section: Introductionmentioning

confidence: 99%

“…It is also known that immune cells can transform into phenotypes that suppress the immune function (M2 phenotype TAMs, N2 TANs), produce anti-inflammatory mediators (NET, IL-10, TGF-β and IL-2) and recruit immunosuppressive cells (T regs , MDSCs, CAFs) that favour potentially malignant cells capable of evading immunity. Moreover, increased angiogenesis mediated by VEGF accelerates the process of carcinogenesis [ 33 , 39 ]. Recent studies clearly indicate that HNSCC patients are characterized by impaired dendritic cells (DCs) and natural killer (NK) cell function, increased production of inhibiting cytokines and immunosuppressive factors, loss of costimulatory molecules and MHC class I molecules, a decrease in the number of regulatory T cell subpopulations, a lower number of lymphocyte subsets and a poor response to antigen-presenting cells [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

Starska

2023

Cancers

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Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive and heterogeneous groups of human neoplasms. HNSCC is characterized by high morbidity, accounting for 3% of all cancers, and high mortality with ~1.5% of all cancer deaths. It was the most common cancer worldwide in 2020, according to the latest GLOBOCAN data, representing the seventh most prevalent human malignancy. Despite great advances in surgical techniques and the application of modern combinations and cytotoxic therapies, HNSCC remains a leading cause of death worldwide with a low overall survival rate not exceeding 40–60% of the patient population. The most common causes of death in patients are its frequent nodal metastases and local neoplastic recurrences, as well as the relatively low response to treatment and severe drug resistance. Much evidence suggests that the tumour microenvironment (TME), tumour infiltrating lymphocytes (TILs) and circulating various subpopulations of immunocompetent cells, such regulatory T cells (CD4+CD25+Foxp3+Tregs), cytotoxic CD3+CD8+ T cells (CTLs) and CD3+CD4+ T helper type 1/2/9/17 (Th1/Th2/Th9/Th17) lymphocytes, T follicular helper cells (Tfh) and CD56dim/CD16bright activated natural killer cells (NK), carcinoma-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (N1/N2 TANs), as well as tumour-associated macrophages (M1/M2 phenotype TAMs) can affect initiation, progression and spread of HNSCC and determine the response to immunotherapy. Rapid advances in the field of immuno-oncology and the constantly growing knowledge of the immunosuppressive mechanisms and effects of tumour cancer have allowed for the use of effective and personalized immunotherapy as a first-line therapeutic procedure or an essential component of a combination therapy for primary, relapsed and metastatic HNSCC. This review presents the latest reports and molecular studies regarding the anti-tumour role of selected subpopulations of immunocompetent cells in the pathogenesis of HNSCC, including HPV+ve (HPV+) and HPV−ve (HPV−) tumours. The article focuses on the crucial regulatory mechanisms of pro- and anti-tumour activity, key genetic or epigenetic changes that favour tumour immune escape, and the strategies that the tumour employs to avoid recognition by immunocompetent cells, as well as resistance mechanisms to T and NK cell-based immunotherapy in HNSCC. The present review also provides an overview of the pre- and clinical early trials (I/II phase) and phase-III clinical trials published in this arena, which highlight the unprecedented effectiveness and limitations of immunotherapy in HNSCC, and the emerging issues facing the field of HNSCC immuno-oncology.

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“…6 The immune microenvironment is complex, in which various immune cells interact with other components, and is closely related to the development and progression of OPMD. 7 Immune cells, such as T cells and macrophages, play major roles in OLK. Alterations of immune cells are associated with epithelial dysplasia and might participate in malignant transformation.…”

Section: Introductionmentioning

confidence: 99%

“…The immune microenvironment is complex, in which various immune cells interact with other components, and is closely related to the development and progression of OPMD 7 . Immune cells, such as T cells and macrophages, play major roles in OLK.…”

Section: Introductionmentioning

confidence: 99%

The preliminary exploration of immune microenvironment in oral leukoplakia concomitant with oral submucosal fibrosis: A comparative immunohistochemical study

Cai

Zhang

Peng

et al. 2023

J Oral Pathology Medicine

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BackgroundOral leukoplakia concomitant with oral submucous fibrosis is a high‐risk oral potentially malignant disorder, but little is known about its immune microenvironment.MethodsThirty samples of oral leukoplakia concomitant with oral submucous fibrosis, 30 oral leukoplakia samples, and 30 oral submucous fibrosis samples were collected from two hospitals. Immunohistochemistry was performed to analyze expression of T cell biomarkers [CD3, CD4, CD8, and Forkhead box P3 (Foxp3)], a B cell biomarker (CD20), macrophage biomarkers (CD68 and CD163), an immune inhibitory receptor ligand (PD‐L1), and Ki‐67.ResultsThe numbers of CD3+ (p < 0.001), CD4+ (p = 0.018), and CD8+ (p = 0.031) cells in oral leukoplakia concomitant with oral submucous fibrosis were less than those in oral leukoplakia. The number of CD4+ cells (p = 0.035) in oral leukoplakia concomitant with oral leukoplakia was higher than that in oral submucous fibrosis. More CD3+(p < 0.001), CD4+(p < 0.001), Foxp3+(p = 0.019), and CD163+(p = 0.029) cells were found in oral leukoplakia than in oral submucous fibrosis.ConclusionVarious levels of immune infiltration were observed among oral leukoplakia concomitant with oral submucous fibrosis, oral leukoplakia, and oral submucous fibrosis. Characterization of the immune microenvironment may contribute to personalized immunotherapy.

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Microenvironment in Oral Potentially Malignant Disorders: Multi-Dimensional Characteristics and Mechanisms of Carcinogenesis

Cited by 10 publications

References 128 publications

TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

The preliminary exploration of immune microenvironment in oral leukoplakia concomitant with oral submucosal fibrosis: A comparative immunohistochemical study

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