The 150 most important questions in cancer research and clinical oncology series: questions 6–14

Cancer, Chinese Journal of

doi:10.1186/s40880-017-0200-0

Cited by 21 publications

(4 citation statements)

References 3 publications

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“…As reported in previous studies, nearly 25% of CRC cases are clinically diagnosed with liver metastasis during initial stage, and approximately 50% of CRC carriers develop liver metastasis symptoms during the course of the disease. Approximately 30-50% of patients with CRC develop recurrent liver metastases after radical resection, and more than 50% among them succumb to the disease 5 . Lungs are the second most common site of distant metastases in CRC 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

MGP promotes CD8⁺ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer

Ding¹,

Sun²,

Zheng³

et al. 2022

Int. J. Biol. Sci.

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Matrix Gla protein (MGP) was originally reported as a physiological suppressor of ectopia calcification and has also been reported to be associated with cancer. However, the relation between the biological functions of MGP and the immune response in colorectal cancer (CRC) remains unclear. Here, we investigated the regulatory role of MGP in the immune microenvironment of CRC. MGP expression in CRC samples was assessed by single-cell RNA sequencing and the Gene Expression Omnibus (GEO) database, and confirmed by quantitative real-time Polymerase Chain Reaction (qRT-PCR) and immunohistochemistry analysis of human CRC samples. The effect of MGP on proliferation and invasion of CRC cells was evaluated by in vitro assays involving MGP knockdown and overexpression. Luciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay were performed to identify transcriptional regulatory sites of the nuclear factor kappa-B (NF-κB) and programmed cell death ligand 1 (PD-L1). In vivo experiments were performed in mouse model of CRC liver metastasis established via spleen injection. The results revealed that MGP was significantly upregulated in cancer cell clusters from the primary CRC or liver metastases, compared with that in the corresponding paracancerous tissues via single-cell RNA sequencing. MGP enriched intracellular free Ca 2+ levels and promoted NF-κB phosphorylation, thereby activated PD-L1 expression to promote CD8 + T cell exhaustion in CRC. The luciferase reporter assay and ChIP-qPCR assay indicated that the transcriptional regulation of NF-κB upregulated PD-L1 expression. In vivo , MGP inhibition significantly decreased the rate of CRC liver metastasis, which was further reduced after combined therapy with αPD1 (anti-PD1). In conclusions, this study revealed that MGP can facilitate CD8 + T cell exhaustion by activating the NF-κB pathway, leading to liver metastasis of CRC. The combination of MGP knockdown and αPD1 can synergistically resist liver metastasis of CRC.

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Section: Introductionmentioning

confidence: 99%

MGP promotes CD8⁺ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer

Ding¹,

Sun²,

Zheng³

et al. 2022

Int. J. Biol. Sci.

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“…Due to its inherent characteristics, distant metastasis (DM) is more commonly observed in NPC than other head and neck squamous cell carcinoma (HNSCC) 5. It is reported that 4–10% of patients with NPC present with synchronous metastasis (smNPC, metastasis at initial diagnosis) 6.…”

Section: Introductionmentioning

confidence: 99%

<p>Characteristic And Novel Therapeutic Strategies Of Nasopharyngeal Carcinoma With Synchronous Metastasis</p>

Liao¹,

Tian²,

Chen³

2019

CMAR

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Nasopharyngeal carcinoma (NPC) is rare in Western countries, but its incidence in China and Southeast Asia is notably high. NPC shows a high rate of distant metastasis including metachronous metastasis (mmNPC, metastasis after definitive chemo-radiotherapy) and synchronous metastasis (smNPC, metastasis at initial diagnosis). 4-10% of patients would be diagnosed as smNPC annually, and the survival outcomes of these patients are quite poor. As with few clinical trials exclusively focusing on this population, treatment on smNPC is not unified and many problems remain unsolved. To date, systematic chemotherapy (CT) still remains a fundamental treatment in smNPC. Although no randomized trial has been conducted to compare different CT regimens in smNPC, gemcitabine and taxanes in combination with platinum seem optimal in first-line setting. In second-line CT, there is no consensus: mono-chemotherapy with drugs such as gemcitabine, taxanes or capecitabine could be taken into consideration. Immunotherapy based on checkpoint inhibitors shows promising efficacy both in first-line and in the following lines of therapy. In addition to CT, local therapy in smNPC is also very important. Locoregional radiotherapy (RT) for primary tumor in combination with CT could strikingly increase OS with acceptable toxicities. And local treatment, such as surgery and RT, for metastatic lesions could bring extra survival benefit in patients with solitary or limited metastases. Overall, the present study provides an overview of the literature on the various studies of smNPC.

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“…NPC is distinct from other head and neck cancers due to its high rates of distant metastasis, including synchronous metastasis (smNPC, metastasis at initial diagnosis) and metachronous metastasis (mmNPC, metastasis over 6 months after radical chemoradiotherapy). 1 – 3 The incidences of smNPC and mmNPC have been reported to be 4%−10% and 15%–30%, respectively. 4 – 6 When metastasis occurs, the survival outcomes of patients are unsatisfactory with a median overall survival (OS) of 12–30 months after multidisciplinary therapies.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study

et al. 2022

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Background: Studies of local therapy (LT) to metastatic foci from nasopharyngeal carcinoma (NPC) are inconsistent and controversial. Here, we aimed to explore the survival benefit of LT directed at metastatic foci from NPC. Methods: A retrospective analysis was conducted in NPC patients with liver, lung, and/or bone metastases. The postmetastatic overall survival (OS) rate was analyzed using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox hazard model. Subgroup analyses evaluating the effect of LT were performed for prespecified covariates. Propensity score matching was applied to homogenize the compared arms. Results: Overall, 2041 of 2962 patients were eligible for analysis. At a median follow-up of 43.4 months, the 5-year OS improved by an absolute difference of 14.6%, from 46.2% in the LT group versus 31.6% in the non-LT group, which led to a hazard ratio of 0.634 for death ( p < 0.001). Matched-pair analyses confirmed that LT was associated with improved OS ( p = 0.003), and the survival benefits of LT remained consistent in the subcohorts of liver and lung metastasis ( p = 0.009 and p = 0.007, respectively) but not of bone metastasis (BoM; p = 0.614). Radiotherapy was predominantly used for BoM and biological effective dose (BED) >60 Gy was found to yield more survival benefit than that of BED ⩽ 60 Gy. Conclusions: The addition of LT directed at metastasis has demonstrated an improvement to OS compared with non-LT group in the present matched-pair study, especially for patients with liver and/or lung metastases.

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The 150 most important questions in cancer research and clinical oncology series: questions 6–14

Cited by 21 publications

References 3 publications

MGP promotes CD8⁺ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer

MGP promotes CD8⁺ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer

<p>Characteristic And Novel Therapeutic Strategies Of Nasopharyngeal Carcinoma With Synchronous Metastasis</p>

Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study

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The 150 most important questions in cancer research and clinical oncology series: questions 6–14

Cited by 21 publications

References 3 publications

MGP promotes CD8+ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer

MGP promotes CD8+ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer

<p>Characteristic And Novel Therapeutic Strategies Of Nasopharyngeal Carcinoma With Synchronous Metastasis</p>

Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study

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MGP promotes CD8⁺ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer

MGP promotes CD8⁺ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer