IL-33/ST2 signaling promotes constitutive and inductive PD-L1 expression and immune escape in oral squamous cell carcinoma

Zhao, Mengxiang; He, Yijia; Zhu, Nisha; Song, Yuxian; Hu, Qingang; Wang, Zhiyong; Ni, Yanhong; Ding, Liang

doi:10.1038/s41416-022-02090-0

Cited by 13 publications

(12 citation statements)

References 41 publications

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“…The protocol of WB was performed as previously described [ 5 ]. Protein samples were isolated by 4–20% SDS-PAGE (smart-Lifesciences).…”

Section: Methodsmentioning

confidence: 99%

“…PBMC was prepared as previously reported [ 5 ]. All study participants provided informed consent and approved by the ethical committee of Nanjing Stomatology Hospital, affiliated Hospital of Medical School, Nanjing University, Nanjing, China.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, discovering new mechanisms and biomarkers to aid in the diagnosis and treatment of OSCC is needed to achieve better patient outcomes. Recently, we previously found that stromal IL-33/ST2 signaling directly or indirectly enhanced PD-L1 (B7-H1)-mediated immune escape [ 4 , 5 ] and also revealed that OXTR + stromal fibroblasts induced high tumor invasion potential and postoperative recurrence in partial OSCC subgroup [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma

He,

Liu,

Dong

et al. 2024

Cancer Immunol Immunother

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Background Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC). Methods PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis. Results Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285–6.851). Conclusions LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.

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“…The protocol of WB was performed as previously described [ 5 ]. Protein samples were isolated by 4–20% SDS-PAGE (smart-Lifesciences).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma

He,

Liu,

Dong

et al. 2024

Cancer Immunol Immunother

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“…Currently, there are 3 major approaches to humanize mice: peripheral blood mononuclear cells (Hu-PBMCs), hematopoietic stem cells (Hu-HSCs), and bone marrow–liver–thymus (Hu-BLT) (De La Rochere et al 2018). Scientists used the Hu-PBMC mouse model to analyze the relationship between IL-33/ST2 signaling and PD-L1 expression in HNSCC patients and cell lines (Zhao et al 2023). They further confirmed this correlation in these humanized mice, demonstrating the role of ST2/PD-L1–mediated immune tolerance in tumor growth in vivo.…”

Section: Transplanted Mouse Model (Xenograft Mouse Models)mentioning

confidence: 99%

Mouse Models for Head and Neck Squamous Cell Carcinoma

Zhou,

Liu,

Amornphimoltham

et al. 2024

J Dent Res

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The prognosis and survival rate of head and neck squamous cell carcinoma (HNSCC) have remained unchanged for years, and the pathogenesis of HNSCC is still not fully understood, necessitating further research. An ideal animal model that accurately replicates the complex microenvironment of HNSCC is urgently needed. Among all the animal models for preclinical cancer research, tumor-bearing mouse models are the best known and widely used due to their high similarity to humans. Currently, mouse models for HNSCC can be broadly categorized into chemical-induced models, genetically engineered mouse models (GEMMs), and transplanted mouse models, each with its distinct advantages and limitations. In chemical-induced models, the carcinogen spontaneously initiates tumor formation through a multistep process. The resemblance of this model to human carcinogenesis renders it an ideal preclinical platform for studying HNSCC initiation and progression from precancerous lesions. The major drawback is that these models are time-consuming and, like human cancer, unpredictable in terms of timing, location, and number of lesions. GEMMs involve transgenic and knockout mice with gene modifications, leading to malignant transformation within a tumor microenvironment that recapitulates tumorigenesis in vivo, including their interaction with the immune system. However, most HNSCC GEMMs exhibit low tumor incidence and limited prognostic significance when translated to clinical studies. Transplanted mouse models are the most widely used in cancer research due to their consistency, availability, and efficiency. Based on the donor and recipient species matching, transplanted mouse models can be divided into xenografts and syngeneic models. In the latter, transplanted cells and host are from the same strain, making syngeneic models relevant to study functional immune system. In this review, we provide a comprehensive summary of the characteristics, establishment methods, and potential applications of these different HNSCC mouse models, aiming to assist researchers in choosing suitable animal models for their research.

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“…The B7 family, a group of 10 structurally related, cell-surface protein ligands, including PD-L1 (B7-H1), encoded by CD274 gene, and inducible T cell costimulatory ligand (ICOSLG, B7-H2), encoded by CD275 gene, bind to receptors on lymphocytes that regulate adaptive immune responses in cancers ( Ni and Dong, 2017 ). PD-L1 (B7-H1) plays a crucial role in immune escape in OSCC ( Zhao et al, 2023 ). The association of ICOSLG expression levels with immunosuppression, tumor progression and prognosis of different solid cancer types such as gastric cancer ( Chen et al, 2003 ), colorectal cancer ( Cao et al, 2018 ) and glioblastoma ( Iwata et al, 2020 ) has been studied.…”

mentioning

confidence: 99%

Editorial: New advancement in tumor microenvironment remodeling and cancer therapy

Yao,

Shen,

Yao

et al. 2024

Front. Cell Dev. Biol.

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IL-33/ST2 signaling promotes constitutive and inductive PD-L1 expression and immune escape in oral squamous cell carcinoma

Cited by 13 publications

References 41 publications

Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma

Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma

Mouse Models for Head and Neck Squamous Cell Carcinoma

Editorial: New advancement in tumor microenvironment remodeling and cancer therapy

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