TIM3+ cells in gastric cancer: clinical correlates and association with immune context

Chen, Ke; Gu, Yun; Cao, Yifan; Fang, Hanji; Lv, Kunpeng; Liu, Xin; He, Xingkang; Wang, Jieti; Lin, Chao; Líu, Hao; Zhang, Heng; He, Hongyong; Xu, Jiejie; Li, He; Li, Ruochen

doi:10.1038/s41416-021-01607-3

Cited by 14 publications

(12 citation statements)

References 38 publications

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“…The results showed that the survival rate and prognosis of PCa patients were lower, and the high expression of FCGR3A and HAVCR2 proteins in PCa tissues increased gradually with the increase of GS when FCGR3A and HAVCR2 were overexpressed. These results were consistent with the findings of FCGR3A and HAVCR2 in other immunological or cancer diseases ( 38 – 41 ). These results suggest that the expression of FCGR3A and HAVCR2 is correlated with the degree of malignancy in PCa patients, and the high expression of FCGR3A and HAVCR2 has a poor prognosis for PCa patients.…”

Section: Discussionsupporting

confidence: 92%

FCGR3A: A new biomarker with potential prognostic value for prostate cancer

et al. 2022

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To screen target gene cluster by bioinformatics analysis and verify them by in vitro experiment and clinicopathological correlation analysis. We try to find a new biomarker with prognostic value for prostate cancer (PCa). 42 candidate marker genes were constructed by protein protein interaction (PPI) network and enriched by KEGG pathway to find out the gene cluster we are interested in. Prognostic model was established to preliminarily analyze the prognostic value of this gene cluster in PCa, and Cox risk regression was used for comparative analysis. Immunohistochemistry was used to detect the expression of each gene in clinical tissue microarray. Finally, we analyzed the correlation between each gene and their clinicopathological features of PCa combined with TCGA clinical data. Based on the analysis of PPI and KEGG, we found the target gene cluster (FCGR3A, HAVCR2, CCR7 and CD28). Prognostic model analysis showed that this gene cluster had the ability to predict biochemical recurrence, and the survival rate and ROC analysis showed favorable prediction effect. Univariate Cox regression analysis showed that the risk scores of Gleason score (GS), T stage, N stage and PSA were significantly different (P<0.05), and the risk ratio of high expression was 2.30 times that of low expression (P=0.004). However, it was not statistically significant in multivariate Cox regression analysis (P>0.05). The results of tissue microarray showed that FCGR3A and HAVCR2 were highly expressed in PCa (P<0.01), while the expression of CCR7 and CD28 had no significant difference (P>0.05). Kaplan-Meier analysis showed that there was significant difference in BCR free survival of FCGR3A and HAVCR2 (FCGR3A, P=0.010; HAVCR2, P=0.018), while the expression of CCR7 and CD28 had no significant difference on the survival and prognosis of PCa patients (P>0.05). TCGA clinical data analysis found that the expression of FCGR3A had a unique correlation with the clinicopathological features of PCa, which was closely related to the tumor stage. The expression of FCGR3A is related to BCR free survival of PCa patients. Therefore, FCGR3A is a new biomarker with potential prognostic value of PCa.

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Section: Discussionsupporting

confidence: 92%

FCGR3A: A new biomarker with potential prognostic value for prostate cancer

et al. 2022

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“… 39 40 One recent study showed that the TIM-3 + cell infiltration was associated with an immunoevasive GC subtype with CD8 + T cell dysfunction and identified that TIM-3 might serve as a promising target for immunotherapy in GC. 41 Another recent study reported that combining anti-PD-1 and anti-TIM-3 mAb had an additive effect on the cytotoxicity of cytotoxic T lymphocytes, suggesting the dual-ICB targeting for PD-1 and TIM-3 as a means of increasing response rates in GC. 42 Based on these findings, triple blockade therapy targeting PD-1, CTLA-4, and TIM-3 might be a rational approach to benefit the patients with EBVaGC with the high density of CTLA-4 + and TIM-3 + cells.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer

Bai

Xie

Wang

et al. 2022

J Immunother Cancer

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BackgroundEpstein-Barr virus (EBV)-associated gastric cancer (GC) (EBVaGC) is a distinct molecular subtype of GC with a favorable prognosis. However, the exact effects and potential mechanisms of EBV infection on immune checkpoint blockade (ICB) efficacy in GC remain to be clarified. Additionally, EBV-encoded RNA (EBER) in situ hybridization (ISH), the traditional method to detect EBV, could cause false-positive/false-negative results and not allow for characterizing other molecular biomarkers recommended by standard treatment guidelines for GC. Herein, we sought to investigate the efficacy and potential biomarkers of ICB in EBVaGC identified by next-generation sequencing (NGS).DesignAn NGS-based algorithm for detecting EBV was established and validated using two independent GC cohorts (124 in the training cohort and 76 in the validation cohort). The value of EBV infection for predicting ICB efficacy was evaluated among 95 patients with advanced or metastatic GC receiving ICB. The molecular predictive biomarkers for ICB efficacy were identified to improve the prediction accuracy of ICB efficacy in 22 patients with EBVaGC.ResultsCompared with orthogonal assay (EBER-ISH) results, the NGS-based algorithm achieved high performance with a sensitivity of 95.7% (22/23) and a specificity of 100% (53/53). EBV status was identified as an independent predictive factor for overall survival and progression-free survival in patients with DNA mismatch repair proficient (pMMR) GC following ICB. Moreover, the patients with EBV+/pMMR and EBV−/MMR deficient (dMMR) had comparable and favorable survival following ICB. Twenty-two patients with EBV+/pMMR achieved an objective response rate of 54.5% (12/22) on immunotherapy. Patients with EBVaGC with a high cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) level were less responsive to anti-programmed death-1/ligand 1 (PD-1/L1) monotherapy, and the combination of anti-CTLA-4 plus anti-PD-1/L1 checkpoint blockade benefited patients with EBVaGC more than anti-PD-1/L1 monotherapy with a trend close to significance (p=0.074). There were nearly significant differences in tumor mutational burden (TMB) level and SMARCA4 mutation frequency between the ICB response and non-response group.ConclusionsWe developed an efficient NGS-based EBV detection strategy, and this strategy-identified EBV infection was as effective as dMMR in predicting ICB efficacy in GC. Additionally, we identified CTLA-4, TMB, and SMARCA4 mutation as potential predictive biomarkers of ICB efficacy in EBVaGC, which might better inform ICB treatment for EBVaGC.

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“…28,29 For instance, in gastric cancer, elevated HAVCR2 expression in tumour tissues is associated with poor prognosis. 29 Similarly in cervical cancer, increased HAVCR2 expression is linked to advanced tumour grades, poor overall survival and metastatic potential. 30 Furthermore, upregulated expression of HAVCR2 has been reported in both OS tissues and cell lines, with this overexpression correlating with poor prognosis in OS patients.…”

Section: Discussionmentioning

confidence: 99%

“…HAVCR2 , also known as a T‐cell immunoglobulin and mucin‐domain‐3‐containing molecule3 ( TIM3 ), belonging to the TIM gene family members of immunoregulatory proteins 27 . Elevated HAVCR2 expression is a recurring phenomenon in cancer cells, it holds predictive power for aggressive disease progression and poor prognosis 28,29 . For instance, in gastric cancer, elevated HAVCR2 expression in tumour tissues is associated with poor prognosis 29 .…”

Section: Discussionmentioning

confidence: 99%

CircPVT1 promotes migration and invasion by regulating miR‐490‐5p/HAVCR2 axis in osteosarcoma cells

Zhou,

Balmer,

Song

et al. 2024

J Cellular Molecular Medi

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Circular RNAs (circRNAs) play an important role in the progression of osteosarcoma. However, the precise function of circPVT1 in osteosarcoma remains elusive. This study aims to explore the molecular mechanism underlying the involvement of circPVT1 in osteosarcoma cells. We quantified circPVT1 expression using qRT‐PCR in both control and osteosarcoma cell lines. To investigate the roles of circPVT1, miR‐490‐5p and HAVCR2 in vitro, we separately conducted overexpression and inhibition experiments for circPVT1, miR‐490‐5p and HAVCR2 in HOS and U2OS cells. Cell migration was assessed through wound healing and transwell migration assays, and invasion was measured via the Matrigel invasion assay. To elucidate the regulatory mechanism of circPVT1 in osteosarcoma, a comprehensive approach was employed, including fluorescence in situ hybridization, qRT‐PCR, Western blot, bioinformatics, dual‐luciferase reporter assay and rescue assay. CircPVT1 expression in osteosarcoma cell lines surpassed that in control cells. The depletion of circPVT1 resulted in a notable reduction in the in vitro migration and invasion of osteosarcoma cells. Mechanism experiments revealed that circPVT1 functioned as a miR‐490‐5p sequester, and directly targeted HAVCR2. Overexpression of miR‐490‐5p led to a significant attenuation of migration and invasion of osteosarcoma cells, whereas HAVCR2 overexpression had the opposite effect, promoting these abilities. Additionally, circPVT1 upregulated HAVCR2 expression via sequestering miR‐490‐5p, thereby orchestrating the migration and invasion in osteosarcoma cells. CircPVT1 orchestrates osteosarcoma migration and invasion by regulating the miR‐490‐5p/HAVCR2 axis, underscoring its potential as a promising therapeutic target for osteosarcoma.

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TIM3+ cells in gastric cancer: clinical correlates and association with immune context

Cited by 14 publications

References 38 publications

FCGR3A: A new biomarker with potential prognostic value for prostate cancer

FCGR3A: A new biomarker with potential prognostic value for prostate cancer

Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer

CircPVT1 promotes migration and invasion by regulating miR‐490‐5p/HAVCR2 axis in osteosarcoma cells

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