Bioinformatics-guided analysis uncovers TIGIT as an epigenetically regulated immunomodulator affecting immunotherapeutic sensitivity of gastric cancer

Ma, Jianfei

doi:10.3233/cbm-210159

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…On the other hand, TIGIT may be a potential target for designing epigenetic drugs. 433 Since TIGIT and PD-1 can be highly co-expressed in CD8 + T cells, 431 TIGIT is expected to be a target for potentiating the benefits of anti-PD-1 therapy.…”

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

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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

View full text Add to dashboard Cite

show abstract

“…The role of epigenetics in TIGIT expression and immunotherapeutic sensitivity was also uncovered in gastric cancer. Increased TIGIT expression in gastric cancer appears to be a favorable event ( 152 ). TIGIT expression correlates with an active immune landscape, survival and immunotherapeutic sensitivity, and favorable prognosis, according to a bioinformatics-guided analysis.…”

Section: Tigit In Cancer Progressionmentioning

confidence: 99%

“…TIGIT expression correlates with an active immune landscape, survival and immunotherapeutic sensitivity, and favorable prognosis, according to a bioinformatics-guided analysis. Patients with high TIGIT expression respond better to immunotherapy than those with low TIGIT expression ( 152 ).…”

Section: Tigit In Cancer Progressionmentioning

confidence: 99%

Update in TIGIT Immune-Checkpoint Role in Cancer

2022

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The in-depth characterization of cross-talk between tumor cells and T cells in solid and hematological malignancies will have to be considered to develop new therapeutical strategies concerning the reactivation and maintenance of patient-specific antitumor responses within the patient tumor microenvironment. Activation of immune cells depends on a delicate balance between activating and inhibitory signals mediated by different receptors. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. TIGIT pathway regulates T cell-mediated tumor recognition in vivo and in vitro and represents an exciting target for checkpoint blockade immunotherapy. TIGIT blockade as monotherapy or in combination with other inhibitor receptors or drugs is emerging in clinical trials in patients with cancer. The purpose of this review is to update the role of TIGIT in cancer progression, looking at TIGIT pathways that are often upregulated in immune cells and at possible therapeutic strategies to avoid tumor aggressiveness, drug resistance, and treatment side effects. However, in the first part, we overviewed the role of immune checkpoints in immunoediting, the TIGIT structure and ligands, and summarized the key immune cells that express TIGIT.

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“…Tyrosine-based inhibition motif domain (TIGIT) is an important immune checkpoint for T/NK cells 25 . It has been found that TIGIT can be detected at breast cancer 26 , renal cell carcinoma 27 , lung adenocarcinoma 28 , hepatocellular carcinoma 29 , gastric cancer 30 , acute myeloid leukemia 31 , melanoma 32 and promote tumor onset, progression and prognosis 33 , 34 . TIGIT is expressed on human tumor-infiltrating CD8+ T cells, NK cells, Th and Treg cells in melanoma 35 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma

Wang,

Ma,

Zhao

et al. 2024

Sci Rep

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Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

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Bioinformatics-guided analysis uncovers TIGIT as an epigenetically regulated immunomodulator affecting immunotherapeutic sensitivity of gastric cancer

Cited by 6 publications

References 32 publications

Signaling pathways and therapeutic interventions in gastric cancer

Signaling pathways and therapeutic interventions in gastric cancer

Update in TIGIT Immune-Checkpoint Role in Cancer

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma

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