T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer

Byun, Kyung Do; Hwang, Hyo Jun; Park, Ki Jae; Kim, Min Chan; Cho, Se Heon; Ju, Mi Ha; Lee, Jin Hwa; Jeong, Jin Sook

doi:10.4048/jbc.2018.21.e61

Cited by 40 publications

(37 citation statements)

References 27 publications

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“…It was reassuring that high‐level expression of TIM‐3 may be a general poor prognostic biomarker in osteosarcoma, gastric cancer, liver cancer, esophageal cancer and lymphoma. Although some findings suggested that high TIM‐3 expression indicated longer OS in breast cancer (HR = 0.11, 95% CI: 0.03‐0.39) 5 and renal cell carcinoma (HR = 0.54, 95% CI: 0.25‐1.17), 6 we found no relationship between TIM‐3 and breast cancer/kidney cancer/lung cancer. The possible reasons might include: (a) the function of TIM‐3 may vary depending upon tumor stages; (b) due to the heterogeneous nature of cancer 4‐6,55 .…”

Section: Discussioncontrasting

confidence: 70%

“…As shown in Figure 1, the initial literature search obtained 2432 articles and a total of 33 studies, 4‐6,12‐18,26‐48 including 4223 patients were finally included after further examination.…”

Section: Resultsmentioning

confidence: 99%

“…T‐cell immunoglobulin mucin‐3 (TIM‐3) is mainly localized on the T‐cell surface as an immune checkpoint (co‐inhibitory signal receptor) 3 . Lots of studies demonstrated that TIM‐3 played a pivotal role in immune modulation of cancers 4‐6 . Moreover, previous research showed that aberrant TIM‐3 expression was central to carcinogenesis and progression 7 .…”

Section: Introductionmentioning

confidence: 99%

“…However, more and more researches have been published to explore the function of TIM‐3 in cancers over the past 5 years, and new evidences have been contrary to previously published studies. Specifically, Burugu et al found that high TIM‐3 expression cancer tissue was associated with good prognosis in patients 4‐6 . Meanwhile, previous research only discussed the prognostic significance of patients' overall survival (OS), 19 and so far, the relationship between high expression of TIM‐3 and certain tumor types remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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“…As indicated by the analysis of KM-plotter database, although Tim-3 is associated with poor prognosis in total breast cancer patients, the prognostic significance is varied in different subtypes. [56] including 109 samples of TNBC [57]. We therefore speculate that the distribution of Tim-3 expression on tumour cells or immune cells might have different prognostic significance, and the major location of Tim-3 in certain types of cells in cancer might determine the prognostic outcomes, although advanced investigation would be required to unveil the paradox of the Tim-3 clinical significance in future.…”

Section: Discussionmentioning

confidence: 99%

Tim-3 promotes cell aggressiveness and paclitaxel resistance through the NF-κB /STAT3 signaling pathway in breast cancer

Cong

Cui

Zhu

et al. 2020

Preprint

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virus cellular receptor 2 (HAVCR2), is a negative immune checkpoint mole cule expressed on a variety of immune cells including T cells [5], dendritic cells [6], and macrophages [7]. Accumulating evidence demonstrate that Tim-3 can reduce cell proliferation, decrease the production of effective cytokines and increase apoptosis of effector T cells, through interaction with its ligands including galectin-9, high mobility group protein B1 (HMGB1), carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM-1) and phosphatidylserine [8,9].Tim-3 is now considered as a critical mediator in cancer pro gression and attracts considerable attention as a therapeutic target. Blocking Tim-3 indeed shows some promising results in multiple preclinical cancer models [10]. More importantly, there is evidence suggesting that resistance to anti-CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) or anti-PD-1/PD-L1 inhibitors is partially by compensatory upregulation of additional immune checkpoints including Tim-3 [11]. And co-blockade of PD-1 and Tim-3 shows a significant survival advantage in a lung cancer mouse model [12]. These findings support the view that Tim-3 may be a potential target for tumour therapy.Interestingly, Tim-3 is not only expressed on immune cells but also overexpressed on many types of malignant tumours. In vitro findings revealed that Tim-3 promoted metastasis of esophageal squamous cell carcinoma (ESCC) by inducing epithelial-mesenchymal transition (EMT) via the Akt/GSK-3/Snail signalling pathway. Tim-3 knockdown markedly inhibited proliferation, migration, and invasion of ESCC cell lines [13]. Additionally, Interfering Tim-3 expression can significantly suppress osteosarcoma cell proliferation and metastasis via the NF-κB/Snail signalling pathway and EMT [14].Recently, a study in liver cancer indicated that tumour cell-intrinsic Tim-3 promotes cell proliferation via the NF-κB/IL-6/STAT3 cascade signalling axis [15]. Clinically, The ectopic expression of Tim-3 in tumour cells were correlated with more advanced pathologic T classification in non-small-cell lung carcinoma [16], lymph-vascular invasion in gastric cancer [17], lung metastasis in clear cell renal cell carcinoma [18], and lymphatic metastasis in colon cancer [9]. A meta-analysis revealed that higher expression of Tim-3 in solid tumours had significantly shorter overall survival [19]. Therefore, Tim-3 has been depicted as a prognostic indicator for those cancer patients. But contradictory results were also reported in terms of the role of Tim-3. Down-regulated Tim-3 promotes invasion and metastasis

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Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival

Guan

Yang

et al. 2019

Intl Journal of Cancer

137

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Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint‐targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan–Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.

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T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer

Cited by 40 publications

References 27 publications

Precision Medical Sciences

Precision Medical Sciences

Tim-3 promotes cell aggressiveness and paclitaxel resistance through the NF-κB /STAT3 signaling pathway in breast cancer

Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival

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