NFκB and TGFβ contribute to the expression of PTPN3 in activated human lymphocytes

Nakayama, Kouji; Onishi, Hideya; Fujimura, Akiko; Imaizumi, Akira; Kawamoto, Makoto; Oyama, Yoshie; Ichimiya, Shu; Koga, Shozo; Fujimoto, Yuichi; Nakashima, Kinichi; Nakamura, Masafumi

doi:10.1016/j.cellimm.2020.104237

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…According to previous reports, PTPN3 is essential for immune checkpoint function in activated lymphocytes, where transcription factor NF-κB enhances PTPN3 expression. On the other hand, TGF-β decreases PTPN3 expression and NF-κB activation in the cancer microenvironment and prevents lymphocytes from functioning biologically [ 21 , 32 ]. Several investigations have demonstrated that PTPN3 is involved in reducing T cell activation and adversely modulating TCR signaling [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy

Zhou,

Lin,

Wang

et al. 2024

Eur J Med Res

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Background The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. Methods The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. Results PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. Conclusions Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.

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Section: Discussionmentioning

confidence: 99%

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy

Zhou,

Lin,

Wang

et al. 2024

Eur J Med Res

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“…SHH is secreted by tumor-infiltrated macrophages through the NF-κB pathway and induces proliferation in a paracrine manner in pancreatic cancer (19). The contribution of NF-κB to cancer-infiltrated lymphocytes has also been reported (134). Collectively, NF-κB significantly contributes to the CME.…”

Section: Nuclear Transcription Factor-κβmentioning

confidence: 96%

Cancer therapy that targets the Hedgehog signaling pathway considering the cancer microenvironment (Review)

et al. 2022

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Recently, the cancer microenvironment (CME) has received significant attention. At the local site of the tumor, cancer progression is affected by secreted cytokines and conditions derived from the CME and stimulation by cancer-induced cytokines in an autocrine manner. The CME is characterized by various types of conditions, such as hypoxia, inflammation stimulation, and angiogenesis, and contains various components, such as reactive oxygen species, cancer-associated fibroblasts, infiltrated immune cells, exosomes, and cancer stem cells (CSCs). These conditions and components complicate the progression of cancer. The Hedgehog (HH) signaling pathway is a morphogenesis signaling pathway that is reactivated in some cancers. In these cancers, reactivated HH signaling is involved in the induction of the malignant phenotype. HH signaling is also activated under hypoxic conditions and is considered to be strongly correlated with the CME, including the induction of cancer fibrosis and maintenance of CSCs. The aim of the present review was to elucidate a cancer therapy that targets HH signaling by considering the CME, particularly focusing on hypoxia.

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NFκB and TGFβ contribute to the expression of PTPN3 in activated human lymphocytes

Cited by 2 publications

References 24 publications

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy

Cancer therapy that targets the Hedgehog signaling pathway considering the cancer microenvironment (Review)

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