Tumor-infiltrating podoplanin
            <sup>+</sup>
            cells in gastric cancer: clinical outcomes and association with immune contexture

Liu, Xin; Cao, Yifan; Lv, Kunpeng; Gu, Yun; Jin, Kaifeng; He, Xingkang; Fang, Hanji; Fei, Yuchao; Shi, Meng; Lin, Chao; Líu, Hao; Li, He; He, Hongyong; Xu, Jiejie; Li, Ruochen; Zhang, Heng

doi:10.1080/2162402x.2020.1845038

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…In preclinical studies, TIM-3 inhibitors showed similar effects to PD-1 inhibitors, and a combination of PD-1 and TIM-3 inhibitors enhances T cell responsiveness to tumor antigens with synergistic effects, suggesting that TIM-3 may be a useful target in treating GC resistant to anti-PD-1 immunotherapy. 426 , 427 The expression of TIM-3 inhibitory ligands on GC cells might also be potential biomarkers for predicting the treatment response of PD-1 mAb. 428 Targeting PD-1 and TIM-3 combination immunotherapy may have more therapeutic benefit than mono-immunotherapy for GC patients.…”

Section: Signaling Pathways In Gastric Cancer and Therapeutic Implica...mentioning

confidence: 99%

Signaling pathways and therapeutic interventions in gastric cancer

Lei

Teng

Chen

et al. 2022

Sig Transduct Target Ther

115

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Gastric cancer (GC) ranks fifth in global cancer diagnosis and fourth in cancer-related death. Despite tremendous progress in diagnosis and therapeutic strategies and significant improvements in patient survival, the low malignancy stage is relatively asymptomatic and many GC cases are diagnosed at advanced stages, which leads to unsatisfactory prognosis and high recurrence rates. With the recent advances in genome analysis, biomarkers have been identified that have clinical importance for GC diagnosis, treatment, and prognosis. Modern molecular classifications have uncovered the vital roles that signaling pathways, including EGFR/HER2, p53, PI3K, immune checkpoint pathways, and cell adhesion signaling molecules, play in GC tumorigenesis, progression, metastasis, and therapeutic responsiveness. These biomarkers and molecular classifications open the way for more precise diagnoses and treatments for GC patients. Nevertheless, the relative significance, temporal activation, interaction with GC risk factors, and crosstalk between these signaling pathways in GC are not well understood. Here, we review the regulatory roles of signaling pathways in GC potential biomarkers, and therapeutic targets with an emphasis on recent discoveries. Current therapies, including signaling-based and immunotherapies exploited in the past decade, and the development of treatment for GC, particularly the challenges in developing precision medications, are discussed. These advances provide a direction for the integration of clinical, molecular, and genomic profiles to improve GC diagnosis and treatments.

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Section: Signaling Pathways In Gastric Cancer and Therapeutic Implica...mentioning

confidence: 99%

Signaling pathways and therapeutic interventions in gastric cancer

Lei

Teng

Chen

et al. 2022

Sig Transduct Target Ther

115

View full text Add to dashboard Cite

show abstract

“…PDPN is expressed in lymphatic endothelial cells, T-help cells (Th17), and broblasts which are reported to participate in chronic in ammatory autoimmune diseases, such as systemic sclerosis and rheumatoid arthritis [10]. With respect to the association between PDPN expression and tumor immunity, PDPN expression helps to identify an immunoevasive context in gastric tumors [35]. Recently, a study reported that PDPN expression was positively associated with tumor-associated macrophages and neutrophils in gliomas and also highlighted that PDPN devoted to constructing an immunosuppressive tumor microenvironment in IDH-wildtype gliomas by promoting macrophage M2 polarization and neutrophil degranulation [12].…”

Section: Discussionmentioning

confidence: 99%

Single-cell and bulk RNA-sequencing analysis reveals heterogeneity of PDPN in predicting prognosis and immunotherapy response of glioma

Lei,

Liu,

Zuo

et al. 2023

Preprint

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Podoplanin (PDPN) is involved in various biological processes of tumors. We sought to investigate the heterogeneity of PDPN expression and the effect of PDPN on the immunological characteristics of gliomas. The signal-cell RNA sequencing (scRNA-seq) data was obtained from the GSE131928 dataset to investigate the heterogeneity of PDPN expression in GBMs. Bulk RNA-seq data of gliomas were obtained from the TCGA, CGGA325, CGGA693, and West China Hospital respectively. CIBERSORTx was used to identify infiltration of immune cells and TIDE was conducted to analyze the immunological function and immune checkpoint inhibitor (ICI) response. PDPN expression was positively associated with the malignancy and served as a predictor for worse overall survival of gliomas. Independent of isocitrate dehydrogenase (IDH) status, PDPN expression was associated with the increased infiltration of immunosuppressive immune cells. scRNA-seq data identified 7 core cell types in glioblastomas (GBMs) and revealed that MES-like GBM cells expressed the highest level of PDPN. AC-like and OPC-like GBM cells had a relatively higher expression of PDPN. Compared to relatively higher PDPN expression in monocytes and macrophages, normal oligodendrocytes and exhausted CD8 + T cells had the lowest level of PDPN. GBM cell clusters with different PDPN levels exhibited distinct functional pathways, such as tumor glycolysis, proliferation, and immune pathways. PDPN-upregulated gliomas were significantly associated with increased T lymphocyte dysfunction and exclusion and were more sensitive to ICI compared to PDPN-downregulated gliomas. Our results indicated that PDPN was heterogeneously expressed in GBMs and may facilitate guiding immunotherapy.

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“…Previous studies showed that the CD8 T effector gene signature was significantly upregulated in MSI-H tumors compared with MSI-L/MSS tumors [ 17 ]. The abundance of podoplanin is related to the immune evasion environment characterized by the infiltration of tumor macrophages and dysfunctional CD8+ T cells [ 18 ]. The growth and progression of tumors are also affected by the abundant tumor-associated macrophages in the tumor microenvironment [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Association between c-type lectin-like receptor 2 and microsatellite instability in colorectal cancer: a cross-sectional study

et al. 2022

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Background As a transmembrane protein, C-type lectin-like receptor 2 (CLEC-2) is mainly expressed on platelets and released into plasma after platelet activation. Activated platelets participate in the regulation of innate immune cells. Patients with different microsatellite statuses have distinct immune profiles. This study aimed to investigate the association of plasma CLEC-2 levels with microsatellite status among colorectal cancer (CRC) patients. Methods A cross-sectional analysis of 430 CRC patients from Harbin Medical University Cancer Hospital was conducted. CLEC-2 levels were measured with fasting venous blood samples drawn from each participant before any treatment. The microsatellite status was evaluated with DNA obtained from fresh frozen tumor tissue samples. The other clinical data were collected and recorded based on the medical system records. Results CLEC-2 levels were significantly higher among patients with high microsatellite instability phenotype than the stable microsatellite group, adjusting for other confounding variables. Conclusions The increased CLEC-2 is associated with the high microsatellite instability subtype of CRC.

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Tumor-infiltrating podoplanin ⁺ cells in gastric cancer: clinical outcomes and association with immune contexture

Cited by 9 publications

References 39 publications

Signaling pathways and therapeutic interventions in gastric cancer

Signaling pathways and therapeutic interventions in gastric cancer

Single-cell and bulk RNA-sequencing analysis reveals heterogeneity of PDPN in predicting prognosis and immunotherapy response of glioma

Association between c-type lectin-like receptor 2 and microsatellite instability in colorectal cancer: a cross-sectional study

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Tumor-infiltrating podoplanin + cells in gastric cancer: clinical outcomes and association with immune contexture

Cited by 9 publications

References 39 publications

Signaling pathways and therapeutic interventions in gastric cancer

Signaling pathways and therapeutic interventions in gastric cancer

Single-cell and bulk RNA-sequencing analysis reveals heterogeneity of PDPN in predicting prognosis and immunotherapy response of glioma

Association between c-type lectin-like receptor 2 and microsatellite instability in colorectal cancer: a cross-sectional study

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Tumor-infiltrating podoplanin ⁺ cells in gastric cancer: clinical outcomes and association with immune contexture