Tumor‐infiltrating lymphocyte‐derived MLL2 independently predicts disease‐free survival for patients with early‐stage oral squamous cell carcinoma

Zhu, Nisha; Ding, Liang; Fu, Yong; Yang, Yan; Chen, Sheng; Chen, Wantao; Zhao, Mengxiang; Zhao, Xingxing; Lu, Zhanyi; Ni, Yanhong

doi:10.1111/jop.12969

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…Staining intensity was defined as 0, negative staining; 1, weak staining; 2, moderate staining and 3, strong staining. Final immunohistochemical scores were calculated by multiplying the percentage score and the intensity score 55 .…”

Section: Sequential Fluorochrome Labelingmentioning

confidence: 99%

Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement

Jin

Ding

et al. 2020

Sci Rep

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Orthodontic force-induced osteogenic differentiation and bone formation at tension side play a pivotal role in orthodontic tooth movement (OTM). Platelet-derived growth factor-BB (PDGF-BB) is a clinically proven growth factor during bone regeneration process with unclear mechanisms. Fibroblasts in periodontal ligament (PDL) are considered to be mechanosensitive under orthodontic force. Thus, we established OTM model to investigate the correlation between PDGF-BB and fibroblasts during bone regeneration at tension side. We confirmed that tensile force stimulated PDL cells to induce osteogenic differentiation via Runx-2, OCN up-regulation, and to accelerate new bone deposition along the periodontium and the alveolar bone interface. Interestingly, PDGF-BB level was remarkably enhanced at tension side during OTM in parallel with up-regulated PDGFRβ+/α-SMA+ fibroblasts in PDL by immunohistochemistry. Moreover, orthodontic force-treated primary fibroblasts from PDL were isolated and, cultured in vitro, which showed similar morphology and phenotype with control fibroblasts without OTM treatment. PDGFRβ expression was confirmed to be increased in orthodontic force-treated fibroblasts by immunofluorescence and flow cytometry. Bioinformatics analysis identified that PDGF-BB/PDGFRβ signals were relevant to the activation of JAK/STAT3 signals. The protein expression of JAK2 and STAT3 was elevated in PDL of tension side. Importantly, in vivo, the treatment of the inhibitors (imatinib and AG490) for PDGFRβ and JAK-STAT signals were capable of attenuating the tooth movement. The osteogenic differentiation and bone regeneration in tension side were down-regulated upon the treatment of inhibitors during OTM. Meanwhile, the expressions of PDGFRβ, JAK2 and STAT3 were inhibited by imatinib and AG490. Thus, we concluded that tensile force-induced PDGF-BB activated JAK2/STAT3 signals in PDGFRβ + fibroblasts in bone formation during OTM. Mechanical forces are integral to bone homeostasis and bone regeneration by driving cell differentiation 1. It was reported that the mechanical force applied during mandible distraction osteogenesis promoted endogenous bone formation across a mechanically controlled environment 2,3. During the process of OTM, the appropriate application of mechanical force promotes alveolar bone remodeling, which consists of bone resorption at compression side and bone formation at tension side of the alveolar bone 4,5 .

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Section: Sequential Fluorochrome Labelingmentioning

confidence: 99%

Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement

Jin

Ding

et al. 2020

Sci Rep

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“…The included studies were conducted in 16 different countries, that is Austria, 23 Brazil, 24 Canada, 25,26 China, 27,28 Denmark, 29,30 France, 31,32 Germany, 33 India, 34–36 Japan, 37 Malaysia, 38 Pakistan, 39 Poland, 40 Taiwan, 41,42 Thailand, 43 the Netherlands, 44 and the United States of America 45–55 . All of them were published in English between 2011 and 2022.…”

Section: Resultsmentioning

confidence: 99%

KMT2 (MLL) family of methyltransferases in head and neck squamous cell carcinoma: A systematic review

da Silva Santos,

de Carvalho Abreu,

Martins da Silva

et al. 2023

Head & Neck

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BackgroundThe involvement of the KMT2 methyltransferase family in the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains elusive.MethodThis study adhered to the PRISMA guidelines, employing a search strategy in the LIVIVO, PubMed, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological quality of the studies was assessed by the Joanna Briggs Institute.ResultsA total of 33 studies involving 4294 individuals with HNSCC were included in this review. The most important alteration was the high mutational frequency in the KMT2C and KMT2D genes, with reported co‐occurrence. The expression of the KMT2D gene exhibited considerable heterogeneity across the studies, while limited data was available for the remaining genes.ConclusionsKMT2C and KMT2D genes seem to have tumor suppressor activities, with involvement of cell cycle inhibitors, regulating different pathways that can lead to tumor progression, disease aggressiveness, and DNA damage accumulation.

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“…From 2005 to 2017, 96 primary OSCC patients were enrolled. The inclusion and exclusion criteria of patients were the same as those of our previous studies ( 18 ). These patients were followed up for 2–60 months, and the median was 39 months.…”

Section: Methodsmentioning

confidence: 99%

Lipid Droplet-Related PLIN2 in CD68+ Tumor-Associated Macrophage of Oral Squamous Cell Carcinoma: Implications for Cancer Prognosis and Immunotherapy

Dong

Zhang

et al. 2022

Front. Oncol.

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BackgroundPLIN2 (adipose differentiation-related protein) belongs to the perilipin family and is a marker of lipid droplets (LDs). Numerous types of tumor exhibit a high PLIN2 level, but its tumorigenic or tumor-suppressive role has been in debate. Recently, LDs serve as innate immune hubs and show antimicrobial capacity. We here aimed to investigate the heterogeneous functions of PLIN2 in the tumor microenvironment and immune regulation.MethodsThis retrospective study included 96 oral squamous cell carcinoma (OSCC) samples and analyzed the spatial distribution of PLIN2 by immunohistochemistry (IHC) and LD level by oil red O staining. A total of 21 serial sections were obtained to analyze the relationship between PLIN2 and immune cells by IHC and immunofluorescence (IF). Single-cell sequencing was used to analyze the cell locations of PLIN2. The values of diagnosis and prognosis of PLIN2 were also evaluated. Tumor Immune Estimation Resource (TIMER), cBioPortal databases, and IHC analysis were used to investigate the relationship between PLIN2 and OSCC immune microenvironment.ResultsPLIN2 was mainly expressed in tumor-infiltrating immunocytes (TIIs) of OSCC. Patients with high PLIN2 harbored more cytoplastic LDs. CD68+ tumor-associated macrophages (TAMs), instead of T cells and B cells, were found to be the main resource of PLIN2 in OSCC stroma and lung, pancreas, prostate, and testis. However, CD56+ NK cells also showed less extent of PLIN2 staining in OSCC. Moreover, patients with a high PLIN2 level in immune cells had a higher TNM stage and were susceptible to postoperative metastasis, but the escalated PLIN2 level in invasive tumor front independently predicted shorter metastasis-free survival. Furthermore, a high PLIN2 presentation in the microenvironment induced immune suppression which was featured as less infiltration of CD8+ T cells and more CD68+ TAMs and Foxp3+ Tregs, accompanied by more immune checkpoint molecules such as CSF1R, LGALS9, IL-10, CTLA-4, and TIGIT.ConclusionCD68+ TAM-derived PLIN2 might participate in regulating immune balance of OSCC patients, which provides new insight into immune checkpoint therapy.

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Tumor‐infiltrating lymphocyte‐derived MLL2 independently predicts disease‐free survival for patients with early‐stage oral squamous cell carcinoma

Cited by 10 publications

References 31 publications

Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement

Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement

KMT2 (MLL) family of methyltransferases in head and neck squamous cell carcinoma: A systematic review

Lipid Droplet-Related PLIN2 in CD68+ Tumor-Associated Macrophage of Oral Squamous Cell Carcinoma: Implications for Cancer Prognosis and Immunotherapy

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