Ectopic Expression of TIM-3 in Lung Cancers

Zhuang, Xianghua; Zhang, Xiaoning; Xia, Xiyan; Zhang, Cuijuan; Liang, Xiaohong; Gao, Lifen; Zhang, Xin; Ma, Chao

doi:10.1309/ajcp9q6ovlvshtmy

Cited by 74 publications

(56 citation statements)

References 29 publications

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“…[27][28][29] While PD-1 was only expressed on tumor cells in 10% of the unpretreated samples, TIM-3 expression was observed on tumor cells in both unpretreated and pretreated samples. More unpretreated samples had TIM-3 C TILs compare with the pretreated, taken into consideration that our number of pretreated samples is rather low.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

et al. 2016

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Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value.To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy). We stained for PD-1, PD-L1, TIM-3, LAG-3, CD4, CD8, CD45RO, granzyme B, FoxP3 and CD68. Furthermore, we analyzed the relationship between the immunological parameters and survival, as well as response to chemotherapy. We found that TIM-3, PD-1 and PD-L1 were expressed on both immune and tumor cells. Strikingly, PD-1 and PD-L1 expression on tumor cells was only seen in unpretreated samples. No LAG-3 expression was observed. CD45RO expression in the stroma was an independent negative predictive factor for response on chemotherapy, while CD4 and TIM-3 expression in lymphoid aggregates were independent prognostic factors for better outcome. Our data propose TIM-3 as a promising new target in mesothelioma. Chemotherapy influences the expression of immune checkpoints and therefore further research on the best combination treatment schedule is required.

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Section: Discussionmentioning

confidence: 99%

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

et al. 2016

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“…The expression of TIM-3 in CD4+ T cells was associated with nodal metastasis and advanced cancer stage [61]. As well as being present in T cells, TIM3 has been reported in NSCLC in 86.7% of NSCLC tumor cells and is associated with T stage and histology and is an independent prognostic factor in NSCLC (relative risk of 4.481; 95% CI, 1.790–11.22) [62]. In preclinical models, the combined inhibition of TIM3 and PD-1 has been reported to be more effective than inhibiting either pathway alone in a range of solid tumors [59,63,64].…”

Section: Co-inhibitory Interactionsmentioning

confidence: 99%

Immunotherapy in the treatment of non-small cell lung cancer

et al. 2014

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Advances in the understanding of the role of the immune system in tumor immunosurveillance have resulted in the recognition that tumors can evade immune destruction via the dysregulation of co-inhibitory or checkpoint signals. This has led to the development of a generation immunotherapeutic agents targeting the immune checkpoint pathway. Recent early phase studies of immune checkpoint modulators, such as CTLA-4, PD-1 and PD-L1 inhibitors in NSCLC have reported promising results with prolonged clinical responses and tolerable toxicity. This article provides an overview of co-stimulatory and inhibitory molecules that regulate the immune response to tumors, recent therapies that have been developed to exploit these interactions and the role of predictive biomarkers in treatment selection.

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“…T cell immunoglobulin mucin-3 (TIM-3), a membrane protein, plays a pivotal role in immune regulation [7]. Current studies have demonstrated a strong correlation between TIM-3 expression and tumor-associated immune suppression.…”

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confidence: 99%

Prognostic implication of TIM-3 in clear cell renal cell carcinoma

Yuan¹,

Jiang²,

Zhao³

et al. 2014

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Clear cell renal carcinoma (ccRCC) is the most common tumor of the kidney.in adults. The prognosis of ccRCC remains unsatisfactory. Recently, T cell immunoglobulin mucin-3 (TIM-3), a novel transmembrane protein, has been implicated in tumor biology. Its role in ccRCC remains unkonwn. The aim of this study was to investigate the roles of TIM-3 as a prognostic marker in patients with ccRCC.TIM-3 protein expression was determined by immunohistochemistry and Western blot from 137 ccRCC tumor samples and adjacent normal renal tissues. We performed also the cell proliferation assay using 3-(4,5-dimethylthiazol -2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human ccRCC cell lines were evaluated. TIM-3 expression was higher in ccRCC tissue than in the adjacent normal renal tissue (P<0.001). High TIM-3 expression was an independent predictor of both cancer-specific survival and progression-free survival. TIM-3 protein was expressed in both ccRCC cell lines. Knockdown of TIM-3 suppressed the proliferation and invasion capacity of ccRCC cell lines.TIM-3 expression was associated with poor prognosis in ccRCC. Taken together, TIM-3 is a potential prognostic marker in ccRCC.

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Ectopic Expression of TIM-3 in Lung Cancers

Cited by 74 publications

References 29 publications

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

Immunotherapy in the treatment of non-small cell lung cancer

Prognostic implication of TIM-3 in clear cell renal cell carcinoma

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