PD-1/PD-L1, Treg-related proteins, and tumour-infiltrating lymphocytes are associated with the development of oral squamous cell carcinoma

Kujan, Omar; Agag, Muhamed; Smaga, Monika; Vaishnaw, Yash; Idrees, Majdy; Shearston, Kate; Farah, Camile S.

doi:10.1016/j.pathol.2021.09.013

Cited by 27 publications

(31 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The transition from OPL to invasive cancer requires that dysplastic lesions escape recognition from infiltrating cytotoxic T lymphocytes (TILs). TILs are increased in OPLs and predict histological grade in dysplastic lesions (12)(13)(14). Comparing lichen planus with oral dysplastic lesions, Flores-Hidalgo et al demonstrated that CD8 + T cells tracked the malignant transformation zones in dysplastic lesions (15).…”

Section: The Evolution Of the Immunosuppressive Microenvironment In Oplmentioning

confidence: 99%

Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy

et al. 2022

View full text Add to dashboard Cite

Oral premalignant lesions (OPLs) are the precursors to oral cavity cancers, and have variable rates of progression to invasive disease. As an intermediate state, OPLs have acquired a subset of the genomic alterations while arising in an oral inflammatory environment. These specific genomic changes may facilitate the transition to an immune microenvironment that permits malignant transformation. Here, we will discuss mechanisms by which OPLs develop an immunosuppressive microenvironment that facilitates progression to invasive cancer. We will describe how genomic alterations and immune microenvironmental changes co-evolve and cooperate to promote OSCC progression. Finally, we will describe how these immune microenvironmental changes provide specific and unique evolutionary vulnerabilities for targeted therapies. Therefore, understanding the genomic changes that drive immunosuppressive microenvironments may eventually translate into novel biomarker and/or therapeutic approaches to limit the progression of OPLs to potential lethal oral cancers.

show abstract

Section: The Evolution Of the Immunosuppressive Microenvironment In Oplmentioning

confidence: 99%

Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The microenvironment of OPMDs means the cells, molecules, and structures (such as blood vessels) that surround and support the cells and tissue of OPMDs. It undergoes changes and promotes the carcinogenesis of OPMDs significantly [ 4 , 5 , 6 , 7 ]. The potentially malignant cells, which refers to the cells that have a potential for carcinogenesis, undergo metabolic reprogramming.…”

Section: Introductionmentioning

confidence: 99%

“…The potentially malignant cells, which refers to the cells that have a potential for carcinogenesis, undergo metabolic reprogramming. It usually inhibits the activation and function of immune cells, and remodels the extracellular matrix (ECM) [ 4 , 6 ]. The immune cells also undergo metabolic reprogramming and remodel the ECM to adapt to adverse conditions [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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

Deng

Wang

Shi

et al. 2022

IJMS

View full text Add to dashboard Cite

Oral potentially malignant disorders (OPMDs) are a group of diseases involving the oral mucosa and that have a risk of carcinogenesis. The microenvironment is closely related to carcinogenesis and cancer progression by regulating the immune response, cell metabolic activities, and mechanical characteristics. Meanwhile, there are extensive interactions between the microenvironments that remodel and provide favorable conditions for cancer initiation. However, the changes, exact roles, and interactions of microenvironments during the carcinogenesis of OPMDs have not been fully elucidated. Here, we present an updated landscape of the microenvironments in OPMDs, emphasizing the changes in the immune microenvironment, metabolic microenvironment, mechanical microenvironment, and neural microenvironment during carcinogenesis and their carcinogenic mechanisms. We then propose an immuno–metabolic–mechanical–neural interaction network to describe their close relationships. Lastly, we summarize the therapeutic strategies for targeting microenvironments, and provide an outlook on future research directions and clinical applications. This review depicts a vivid microenvironment landscape and sheds light on new strategies to prevent the carcinogenesis of OPMDs.

show abstract

“…The intricate interplay between tumor cells and surrounding TME cells leads to malignant evolution of oral premalignant lesions and adverse prognosis of OSCC patients [ 7 , 8 ]. For example, Kujan et al found significant positive associations between regulatory T cell (Treg)-related proteins (including FOXP3, TGF-β, IL-6, and IL-10) and the histopathological grade of oral epithelial disorders, implying a possible role of tumor-infiltrating immune cells play in evading the immune system and potentially driving malignant transformation [ 9 ]. Macrophages are phagocytic and antigen-presenting cells of innate immune system.…”

Section: Introductionmentioning

confidence: 99%

CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma

et al. 2022

View full text Add to dashboard Cite

Purpose This study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). Methods We analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro. Results In OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro. Conclusion CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.

show abstract

PD-1/PD-L1, Treg-related proteins, and tumour-infiltrating lymphocytes are associated with the development of oral squamous cell carcinoma

Cited by 27 publications

References 44 publications

Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy

Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy

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

CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma

Contact Info

Product

Resources

About