Expression of immune checkpoints in T cells of esophageal cancer patients

Xie, Jin-hua; Wang, Ji; Cheng, Shouliang; Zheng, Liangfeng; Ji, Feiyue; Yang, Lin; Zhang, Yan; Ji, Hong

doi:10.18632/oncotarget.11611

Cited by 36 publications

(28 citation statements)

References 15 publications

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“…In addition, among CD4 + TIL, TIM-3 is preferentially expressed on Foxp3 + CD4 + Treg cells, and the frequency of CD4 + TIM-3 + TIL is correlated with poor patient survival [54]. TIM-3 was also shown to be expressed in TIL or tumor antigen-specific T cells in peripheral blood from many cancer types such as hepatocellular cancer, cervical cancer, colorectal cancer, ovarian cancer [55], NSCLC [56,57], head and neck cancer [58], renal cell carcinoma (RCC) [59], gastric cancer [60], esophageal cancer [61], prostate cancer [62], and non-Hodgkin lymphoma [63]. …”

Section: Tim-3 In Immune Tolerance To Tumorsmentioning

confidence: 99%

TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action

Yang

Turner

et al. 2017

IJMS

193

150

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Abstract:Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy. Despite a large amount of experimental data showing an immune suppressive function of TIM-3 in vivo, the exact mechanisms are not well understood. To enable effective targeting of TIM-3 for tumor immunotherapy, further in-depth mechanistic studies are warranted. These studies will also provide much-needed insight for the rational design of novel combination therapy with other checkpoint blockers. In this review, we summarize key evidence supporting an immune regulatory role of TIM-3 and discuss possible mechanisms of action.

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Section: Tim-3 In Immune Tolerance To Tumorsmentioning

confidence: 99%

TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action

Yang

Turner

et al. 2017

IJMS

193

150

View full text Add to dashboard Cite

show abstract

“…Tumor-infiltrating CD4 and CD8 cells co-express TIM-3 and PD-1 in murine models of colon adenocarcinoma, melanoma and mammary adenocarcinoma (Assal et al 2015). In humans, TIM-3 is expressed on tumorinfiltrating lymphocytes or T cells in the peripheral blood of patients with various types of cancer such as hepatocellular cancer, cervical cancer, colorectal cancer, ovarian cancer, non-small-cell lung cancer, head and neck cancer, renal cell carcinoma, gastric cancer, esophageal cancer, prostate cancer and non-Hodgkin lymphoma (Yang et al 2012, Jie et al 2013, Yan et al 2013, Japp et al 2015, Thommen et al 2015, Cai et al 2016, Xie et al 2016. Preclinical models show conflicting results for the administration of TIM-3-targeting monoclonal antibody.…”

Section: Lag-3 Also Called Cd223 Lag-3 Is Expressed On Activated T Cmentioning

confidence: 99%

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Cunha

Marcello

Rocha-Santos

et al. 2017

Endocrine-Related Cancer

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Immune checkpoint inhibitors are agents that act by inhibiting the mechanisms of immune escape displayed by various cancers. The success of immune checkpoint inhibitors against several tumors has promoted a new treatment strategy in clinical oncology, and this has encouraged physicians to increase the number of patients who receive the immune checkpoint therapy. In the present article, we review the main concepts regarding immune checkpoint mechanisms and how cancer disrupts them to undergo immune escape. In addition, we describe the most essential concepts related to immune checkpoint inhibitors. We critically review the literature on preclinical and clinical studies of the immune checkpoint inhibitors as a treatment option for thyroid cancer, ovarian carcinoma, pancreatic adenocarcinoma, adrenocortical carcinoma and neuroendocrine tumors. We present the challenges and the opportunities of using immune checkpoint inhibitors against these endocrine malignancies, highlighting the breakthroughs and pitfalls that have recently emerged.

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“…Immune exhaustion, a state in which T cells become functionally inept, is a common feature of many tumors, including HNSCC. 68,69 Similarly to immune checkpoint inhibitors such as pembrolizumab, metformin has been shown to reverse immune exhaustion. 70,71 Interestingly, metformin has been shown to potentiate the anticancer effects of other drugs, including antimetabolites and tyrosine kinase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Metformin effects on head and neck squamous carcinoma microenvironment: Window of opportunity trial

Curry¹,

Johnson²,

Tassone³

et al. 2017

The Laryngoscope

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Objective The tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in HNSCC. We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors. Study Design Window of opportunity trial of metformin between diagnostic biopsy and resection. Participants were patients with newly diagnosed HNSCC. 50 patients were enrolled, and 39 completed a full treatment course. Metformin was titrated to standard diabetic dose (2000 mg/day) for a course of 9 or more days prior to surgery. Level of Evidence 4 Methods Immunohistochemistry (IHC) for the metabolic markers caveolin-1 (CAV1), B-galactosidase (GALB) and monocarboxylate transporter 4 (MCT4) as well as the TUNEL apoptosis assay and Ki-67 IHC were performed in pre- and post-metformin specimens. Exploratory mass spectroscopy imaging (MSI) to assess lactate levels was also performed in three subjects. Results Metformin was well tolerated. The average treatment course was 13.6 days. Post-treatment specimens showed a significant increase in stromal CAV1 (p<0.001) and GALB (p<0.005) and tumor cell apoptosis by TUNEL assay (p<0.001). There was no significant change in stromal MCT4 expression or proliferation measured by Ki67. Lactate levels in carcinoma cells were increased 2.4-fold post-metformin (p<0.05) as measured by MSI. Conclusions Metformin increases markers of reduced catabolism and increased senescence in stromal cells and increased carcinoma cell apoptosis. This study demonstrates that metformin modulates metabolism in the HNSCC microenvironment. Trial Registration ClinicalTrials.gov Identifier NCT02083692.

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Expression of immune checkpoints in T cells of esophageal cancer patients

Cited by 36 publications

References 15 publications

TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action

TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Metformin effects on head and neck squamous carcinoma microenvironment: Window of opportunity trial

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