Tumor-infiltrating γδT cells predict prognosis and adjuvant chemotherapeutic benefit in patients with gastric cancer

Wang, Jieti; Lin, Chao; Li, He; Li, Ruochen; Wu, Yifan; Líu, Hao; Zhang, Heng; He, Hongyong; Zhang, Weijuan; Xu, Jiejie

doi:10.1080/2162402x.2017.1353858

Cited by 44 publications

(26 citation statements)

References 58 publications

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“…TIICs, as well as the chemokines and cytokines secreted by TIICs, are key regulators of antitumor immune responses (Rohr-Udilova et al, 2018). Previous studies have shown that TIICs, such as lymphocytes, gamma delta T cells, regulatory T cells and macrophages, are significantly associated with the prognosis of GC patients (Zhang et al, 2019; Lee et al, 2018; Yu et al, 2018; Wang et al, 2017; Kang et al, 2017; Jiang et al, 2017; Li et al, 2017; Choi et al, 2016). In addition, Peng et al (2017) found that NK-cell function in human GC is impaired by monocytes and macrophages in TME and restoring the function of NK cells could prevent GC tumor immune escape.…”

Section: Discussionmentioning

confidence: 99%

The landscape and prognostic value of tumor-infiltrating immune cells in gastric cancer

Ouyang

Wang

et al. 2019

PeerJ

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Background Gastric cancer (GC) is the fourth most frequently diagnosed malignancy and the second leading cause of cancer-associated mortality worldwide. The tumor microenvironment, especially tumor-infiltrating immune cells (TIICs), exhibits crucial roles both in promoting and inhibiting cancer growth. The aim of the present study was to evaluate the landscape of TIICs and develop a prognostic nomogram in GC. Materials and Methods A gene expression profile obtained from a dataset from The Cancer Genome Atlas (TCGA) was used to quantify the proportion of 22 TIICs in GC by the CIBERSORT algorithm. LASSO regression analysis and multivariate Cox regression were applied to select the best survival-related TIICs and develop an immunoscore formula. Based on the immunoscore and clinical information, a prognostic nomogram was built, and the predictive accuracy of it was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and the calibration plot. Furthermore, the nomogram was validated by data from the International Cancer Genome Consortium (ICGC) dataset. Results In the GC samples, macrophages (25.3%), resting memory CD4 T cells (16.2%) and CD8 T cells (9.7%) were the most abundant among 22 TIICs. Seven TIICs were filtered out and used to develop an immunoscore formula. The AUC of the prognostic nomogram in the TCGA set was 0.772, similar to that in the ICGC set (0.730) and whole set (0.748), and significantly superior to that of TNM staging alone (0.591). The calibration plot demonstrated an outstanding consistency between the prediction and actual observation. Survival analysis revealed that patients with GC in the high-immunoscore group exhibited a poor clinical outcome. The result of multivariate analysis revealed that the immunoscore was an independent prognostic factor. Discussion The immunoscore could be used to reinforce the clinical outcome prediction ability of the TNM staging system and provide a convenient tool for risk assessment and treatment selection for patients with GC.

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Section: Discussionmentioning

confidence: 99%

The landscape and prognostic value of tumor-infiltrating immune cells in gastric cancer

Ouyang

Wang

et al. 2019

PeerJ

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“…84 While results from CRC cohorts receiving chemotherapy are under-reported, a series (n=463) of patients with gastric cancer receiving adjuvant 5-FU chemotherapy suggest a significant survival advantage of chemotherapy versus observation if infiltrating γδ T cells were increased. 85…”

Section: Gamma Delta (γδ) T Cellsmentioning

confidence: 99%

Tumour immune microenvironment biomarkers predicting cytotoxic chemotherapy efficacy in colorectal cancer

Wilkinson

Roberts

et al. 2021

J Clin Pathol

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The role of the local tumour and stromal immune landscape is increasingly recognised to be important in cancer development, progression and response to therapy. The composition, function, spatial orientation and gene expression profile of the infiltrate of the innate and adaptive immune system at the tumour and surrounding tissue has an established prognostic role in colorectal cancer (CRC). Multiple studies have confirmed that a tumour immune microenvironment (TIME) reflective of a type 1 adaptive immune response is associated with improved prognosis. There have been significant efforts to evolve these observations into validated, histopathology-based prognostic biomarkers, such as the Immunoscore. However, the clinical need lies much more in the development of predictive, not prognostic, biomarkers which have the potential to improve patient outcomes. This is particularly pertinent to help guide cytotoxic chemotherapy use in CRC, which remains the standard of care. Cytotoxic chemotherapy has recognised immunomodulatory activity distinct from its antimitotic effects, including mechanisms such as immunogenic cell death (ICD) and induction/inhibition of key immune players. Response to chemotherapy may differ with regard to molecular subtype of CRC, which are strongly associated with immune phenotypes. Thus, immune markers are potentially useful, though under-reported, predictive biomarkers. In this review, we discuss the impact of the TIME on response to cytotoxic chemotherapy in CRC, with a focus on baseline immune markers, and associated genomic and transcriptomic signatures.

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“…Our and others' studies showed that γδT cells have important roles in tumor immunosurveillance against multiple malignancies such as colorectal cancer and leukemia [29,49]. Importantly, tumor-in ltrating γδT cells were an independent prognostic factor in GC patients and could predict the survival bene t of adjuvant chemotherapy in patients with TNM II and III diseases [50]. Therefore, we explored the effect of CM from stable knockdown H19 GC cells on γδT cells.…”

Section: Discussionmentioning

confidence: 98%

H19 contributes to aerobic glycolysis, proliferation and immune escape of gastric cancer cells via the miR-519d-3p/LDHA axis

Sun

Yan³

et al. 2020

Preprint

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Background Long non-coding RNAs (lncRNAs) have been investigated in multiple human cancers including gastric cancer (GC). Our research aims to explore the role of H19 in aerobic glycolysis, proliferation, and immune escape of GC cells.Methods The expression of H19 in GC samples were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA), Gene Expression Omnibus (GEO) data, and real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Glucose consumption and lactate production were applied to assess the aerobic glycolysis of GC cells. Subcellular fractionation, luciferase reporter, and western blot assays certified the binding between genes. CCK-8 and colony formation assays were used to determine GC cell proliferation. Flow cytometry, ELISA, and RT-qPCR assays were applied to analyze the immunosuppressive effect of H19. Results H19 was highly expressed in samples of patients with GC, and associated with tumor growth in vivo. H19 knockdown suppressed glucose consumption, lactate production, proliferation of GC cells by regulating miR-519d-3p/LDHA axis. Both miR-519d-3p depletion and LDHA overexpression could reverse the H19 knockdown-induced decrease in aerobic glycolysis and proliferation. Moreover, conditioned medium (CM) from stable knockdown H19 GC cells modulated the activity of immune cells including γδT cells, Jurkat cells, and tumor-associated macrophages (TAMs) in a lactate dependent manner.Conclusions The H19/miR-519d-3p/LDHA axis mainly contributed to aerobic glycolysis, proliferation, and immune escape of GC cells.

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Tumor-infiltrating γδT cells predict prognosis and adjuvant chemotherapeutic benefit in patients with gastric cancer

Cited by 44 publications

References 58 publications

The landscape and prognostic value of tumor-infiltrating immune cells in gastric cancer

The landscape and prognostic value of tumor-infiltrating immune cells in gastric cancer

Tumour immune microenvironment biomarkers predicting cytotoxic chemotherapy efficacy in colorectal cancer

H19 contributes to aerobic glycolysis, proliferation and immune escape of gastric cancer cells via the miR-519d-3p/LDHA axis

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