Tim-3 and Tim-4 as the potential targets for antitumor therapy

Cheng, Lin; Ruan, Zhihua

doi:10.1080/21645515.2015.1056953

Cited by 46 publications

(40 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Through the GEP analysis in this study, some differential expression genes were revealed in the concordant BM group: high expression level of metabolism-related genes and transcription-activating genes may reflect a high proliferation potency of lymphoma cells; although genes associated with cellular adhesion or migration have not often been described in lymphoma, such a signature in the metastases of solid tumors is well-established; 37 TIMD4 is a member of the T-cell immunoglobulin and mucin domain gene family, which plays a critical role in immunoregulation, and a high level of TIMD4 has been reported as a negative regulator of antitumor immunity. 38 Therefore, a potential molecular basis underlying the development of concordant BM disease may be related to tumor proliferation, cellular adhesion or migration, and immune tolerance or escape.…”

Section: Discussionmentioning

confidence: 99%

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

et al. 2017

View full text Add to dashboard Cite

In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positive and 449 with negative BM status. Compared with negative BM disease, concordant BM adversely impacted overall and progression-free survival, probably independent of the International Prognostic Index (IPI) and cell-of-origin classification. Once BM is concordantly involved, poor prognosis was not associated with the extent of BM involvement. Conversely, patients with discordant BM showed favorable overall survival similar to stage I-II DLBCL. A BM-adjusted IPI, using three parameters: concordant BM involvement, age >60 years, and performance status >1, improves the risk stratification for DLBCL with positive BM. Intensive immunochemotherapy seemingly rendered survival benefit for patients with concordant BM, as did rituximab maintenance for the discordant BM group. Frequently revealing adverse clinical and molecular characteristics, patients with concordant BM demonstrated gene expression signatures relevant to tumor cell proliferation, migration, and immune escape. In conclusion, clinical and biological heterogeneity is seen in DLBCL with positive BM but concordant BM involvement represents a distinct subset with unfavorable gene signatures, high-risk clinicopathologic features, and poor prognosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Experimental models of tumor revealed that combined treatment with anti-Tim-3 and anti-Tim-4 mAbs increased the efficacy of cancer vaccines (76). In accordance, Jinushi et al revealed that a secreted PS-binding protein MFG-E8 blockade also favored the establishment of an immunogenic tumor microenvironment (77).…”

Section: Tumormentioning

confidence: 91%

Tim-4 in Health and Disease: Friend or Foe?

Liang

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

T-cell immunoglobulin and mucin domain containing 4 (Tim-4) is a phosphatidylserine receptor and is selectively expressed on antigen presenting cells. Recently, Tim-4 was reported to be expressed on iNKT cells, B1 cells, and tumor cells, suggesting it has multiple biological functions. In this review, we mainly summarize the expression and regulation of Tim-4 in immune cells including T cells, macrophages, dendritic cells, NKT cells, B cells, and mast cells. The expression of Tim-4 in these cells implies that Tim-4 might participate in immune related diseases. Emerging evidence emphasizes a substantial role for Tim-4 in maintaining homeostasis by regulating various immune responses, including viral infection, allergy, autoimmunity, and tumor immunity. Here, we collectively evaluated the role of Tim-4 in health and diseases. This summary will be extremely useful to fully understand the function of Tim-4 in the pathogenesis of immune related diseases, which would provide novel clues for the diagnosis and treatment of diseases.

show abstract

“…Taken together, these results demonstrate that Tim-3 was expressed in the Th1 and synovial cells of patients with RA. In addition, Tim-3 overexpression may promote the activation and proliferation of tumor cells and macrophages (25)(26)(27). The present study also conducted a MTT assay to detect the effects of Tim-3 siRNA on the LPS-induced proliferation of FLS.…”

Section: Discussionmentioning

confidence: 99%

Effects of Tim-3 silencing on the viability of fibroblast-like synoviocytes and lipopolysaccharide-induced inflammatory reactions

Long

Chen

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. The objective of the present study was to investigate the effects of Tim-3 silencing on cell viability and lipopolysaccharide (LPS)-induced inflammatory reactions in fibroblast-like synoviocytes (FLS). T-cell immunoglobulin mucin domain molecule (Tim)-3 expression in FLS obtained from patients with rheumatoid arthritis (RA) and normal controls were detected by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Small interfering (si)RNA was transfected using Lipofectamine ® 2000 to decrease Tim-3 expression. Following transfection, FLS were stimulated by LPS. An MTT assay, RT-PCR and western blot analysis were performed to measure cell viability, Toll-like receptor 4 (TLR4) signaling pathway-related protein expression and inflammatory cytokine release, respectively. The results of the present study indicated that Tim-3 expression was increased in FLS from patients with RA compared with FLS from healthy controls. Transfection of Tim-3 siRNA significantly decreased Tim-3 expression in FLS from patients with RA. Notably, Tim-3 silencing decreased FLS cell viability. Following stimulation with LPS, cell viability and the expression of TLR4, myeloid differentiation protein gene 88 (MyD88) and nuclear factor-κB (NF-κB) p65 were enhanced in FLS. By contrast, Tim-3 silencing attenuated LPS-induced cell proliferation and the expression of TLR4, MyD88 and NF-κB p65. In addition, LPS significantly increased levels of cytokines in the supernatant, including tumor necrosis factor-α, interferon-γ and interleukin-6 (P<0.01). By contrast, Tim-3 silencing significantly decreased LPS-induced cytokine release (P<0.01). However, Tim-3 silencing did not affect TLR4, MyD88 and NF-κB p65 expression and the release of cytokines in cells that did not undergo treatment with LPS. Therefore, the results of the present study indicate that Tim-3 silencing decreases the viability of FLS in RA and attenuates the LPS-induced inflammatory reaction.

show abstract

Tim-3 and Tim-4 as the potential targets for antitumor therapy

Cited by 46 publications

References 45 publications

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

Tim-4 in Health and Disease: Friend or Foe?

Effects of Tim-3 silencing on the viability of fibroblast-like synoviocytes and lipopolysaccharide-induced inflammatory reactions

Contact Info

Product

Resources

About