High blood levels of soluble OX40 (CD134), an immune costimulatory molecule, indicate reduced survival in patients with advanced colorectal cancer

Sawada, Ryoichi; Arai, Yoshinori; Sagawa, Yukiko; Nagata, Yusuke; Nishimura, Takashi; Noguchi, Masaaki; Amano, Katsushi; Arihiro, Seiji; Saruta, Masayuki; Homma, Sadamu

doi:10.3892/or.2019.7304

Cited by 16 publications

(23 citation statements)

References 28 publications

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“…A few studies have been conducted on the serum levels of OX40 in different malignancies. Adult patients of T-cell leukemia demonstrated elevated serum OX40 levels while Sawada et al reported an association between higher serum levels of OX40 and reduced survival time in advanced stage colorectal patients (n=22) [ 12 - 13 ]. Similarly, Kashima et al in advanced lung adenocarcinoma (n=56) reported higher levels were associated with poor prognosis [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of OX40 in Early and Late-Stage Oral Squamous Cell Carcinoma

Sani¹,

Rubab²,

Usman³

et al. 2021

Cureus

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BackgroundThe tumor necrosis factor receptor superfamily, member 4 (OX40) and its ligand (OX40L) are members of the tumor necrosis factor superfamily and play roles as costimulatory immunomodulators to combat infectious diseases as well as cancers. Presently, many therapeutic agents focused on OX40 and OX40L are in trials for antitumor efficacy. In Pakistan, oral squamous cell carcinoma (OSCC) is the second most prevalent cancer with a mortality of 50% despite the availability of various therapeutic modalities. Data regarding serum levels of OX40 in patients with OSCC is lacking. Therefore, the study aimed to assess the OX40 levels in serum and their association with the clinicopathological features of the tumor. MethodologyA cross-sectional study was conducted and serum samples of 78 biopsy-confirmed OSCC patients were collected prior to any treatment along with 10 healthy persons after informed consent. Serum levels of OX40 were measured via sandwich enzyme-linked immunosorbent assay (ELISA). ResultsThe mean serum levels of OX40 were 1.65 ± 0.64 ng/ml and 2.39 ± 0.58 ng/ml in early and late-stage disease patients of OSCC, respectively (p =<0.005). However, based on gender and tumor site, male gender and buccal mucosa tumors in late-stage OSCC patients showed higher mean levels of OX40, 2.42± 0.58 ng/ml and 2.41 ± 0.58 ng/ml (p =<0.05), respectively. Patients with well-differentiated tumors demonstrated mean serum levels of 2.28 ng/ml, and in moderately differentiated tumors, the mean levels were 2.19 ng/ml (p =0.47). ConclusionsA high OX40 level is associated with advanced-stage disease and a poor prognosis, possibly reflecting the immune-exhausted status against OSCC.

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Section: Discussionmentioning

confidence: 99%

Serum Levels of OX40 in Early and Late-Stage Oral Squamous Cell Carcinoma

Sani¹,

Rubab²,

Usman³

et al. 2021

Cureus

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“…15 16 OX40 is expressed frequently in breast cancer, melanoma, head and neck cancer, colon cancer, and B cell lymphoma cells. [17][18][19] The signals from the binding of OX40 and its ligand promote effector T-cell expansion and survival by enhancing the expression of cyclin A, cyclin-dependent kinases, Bcl-2 antiapoptotic molecules, multiple cytokines and related receptors like interleukin (IL)-2. 20 In addition, OX40 signaling promotes the generation of memory T cells and inhibits the function of Tregs.…”

Section: Ox40mentioning

confidence: 99%

T-cell agonists in cancer immunotherapy

Choi

Shi

Haymaker

et al. 2020

J Immunother Cancer

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Cancer cells can evade immune surveillance in the body. However, immune checkpoint inhibitors can interrupt this evasion and enhance the antitumor activity of T cells. Other mechanisms for promoting antitumor T-cell function are the targeting of costimulatory molecules expressed on the surface of T cells, such as 4-1BB, OX40, inducible T-cell costimulator and glucocorticoid-induced tumor necrosis factor receptor. In addition, CD40 targets the modulation of the activation of antigen-presenting cells, which ultimately leads to T-cell activation. Agonists of these costimulatory molecules have demonstrated promising results in preclinical and early-phase trials and are now being tested in ongoing clinical trials. In addition, researchers are conducting trials of combinations of such immune modulators with checkpoint blockade, radiotherapy and cytotoxic chemotherapeutic drugs in patients with advanced tumors. This review gives a comprehensive picture of the current knowledge of T-cell agonists based on their use in recent and ongoing clinical trials.

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“…It was demonstrated that the combination of CXCL12 with CXCR4 and CXCR7 on tumor cells leads to antiapoptotic signals upregulated by Bcl‐2 and survivin, and affects the progression of gastrointestinal tumors 34 . The soluble TNFSF4 in the blood is positively correlated with carbohydrate antigen (CA) 19‐9, carcinoembryonic antigen, C‐reactive protein, and soluble programmed cell death ligand‐1 in patients with CRC 35 . These results indicate a strong correlation between Syk and immune features.…”

Section: Discussionmentioning

confidence: 98%

Comprehensive analysis of Syk gene methylation in colorectal cancer

Zhu

Liu

et al. 2021

Immunity Inflam & Disease

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Background: Metastasis of colorectal cancer (CRC) extremely affects the prognosis of CRC patients. Recently, the genetic methylation has been shown to associate with tumor metastasis. This research aimed to explore the Syk gene, which is frequently hypermethylated in different cancers, and its impact on the metastasis of CRC cells. Methods: We employed the UALCAN database for the detection of the methylation levels of Syk in different cancers. CIBERSORT, TIMER and TISIDB tools were employed to analyze the association of Syk expression with immune features of CRC. Treatment with decitabine has been noted to restore the expression of Syk in CRC cells. The invasion and migration abilities of CRC cell lines were determined using transwell and wound healing assays. The correlation between Syk and c‐Myc was established using the GEPIA2 database and Western blot assays. Results: Our results, based on UALCAN, revealed that the methylation level of Syk was altered in diverse cancers including colon adenocarcinoma. We found that expression profile and methylation level of Syk was correlated with immune features of colon adenocarcinoma. Decitabine can restore the expression of Syk in HCT116 and SW480 cells, hence affecting their migration and invasion. Results from GEPIA2 showed that Syk expression was correlated with c‐Myc, while Western blotting analysis revealed a negative association between the expression level of Syk and c‐Myc. Conclusions: This study demonstrates that the expression of Syk could be restored by decitabine in colorectal cancer, thus affecting the migration and invasion abilities of CRC cells.

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High blood levels of soluble OX40 (CD134), an immune costimulatory molecule, indicate reduced survival in patients with advanced colorectal cancer

Cited by 16 publications

References 28 publications

Serum Levels of OX40 in Early and Late-Stage Oral Squamous Cell Carcinoma

Serum Levels of OX40 in Early and Late-Stage Oral Squamous Cell Carcinoma

T-cell agonists in cancer immunotherapy

Comprehensive analysis of Syk gene methylation in colorectal cancer

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