Clinical Significance of Serum Soluble T Cell Regulatory Molecules in Clear Cell Renal Cell Carcinoma

Masuda, Akinori; Arai, Kyoko; Nishihara, Daisaku; Mizuno, Tomoya; Yano, Hideo; Kambara, Tsunehito; Betsunoh, Hironori; Abe, Hideyuki; Yashi, Masahiro; Fukabori, Yoshitatsu; Yoshida, Ken; Kamai, Takao

doi:10.1155/2014/396064

Cited by 20 publications

(18 citation statements)

References 36 publications

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“…and Zhao et al . also reported that the serum sB7‐H3 level was significantly related to the clinical stage in clear cell renal cell carcinoma and hepatocellular carcinoma . However, we have not found previous studies reporting the correlation between sB7‐H3 level in serum and B7‐H3 expression in tumor samples.…”

Section: Discussioncontrasting

confidence: 69%

“…29 Masuda et al and Zhao et al also reported that the serum sB7-H3 level was significantly related to the clinical stage in clear cell renal cell carcinoma and hepatocellular carcinoma. 30,31 However, we have not found previous studies reporting the correlation between sB7-H3 level in serum and B7-H3 expression in tumor samples. As sB7-H3 level in serum is a feasible biomarker for prognosis, it should be considered how to use soluble protein in serum to predict prognosis and treatment response in further work.…”

Section: Discussionmentioning

confidence: 69%

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A B7‐CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma

Zheng

Luo

Dong

et al. 2018

Intl Journal of Cancer

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B7 family ligands and CD28 family receptors have complicated interaction for modulating immune functions. They play a central role in response to immunotherapy and outcome of patients with lung adenocarcinoma (LUAD). Thus, we analyzed B7-CD28 family gene expression profiles in LUAD and generated a signature to predict prognosis and immune host status. B7-CD28 family gene expression profiles and clinical data of LUAD from The Cancer Genome Atlas (TCGA) were analyzed. In the training cohort, prognostic association was assessed and then a prognostic signature was built with stepwise multivariable Cox analysis. The signature was validated by Kaplan-Meier and multivariable Cox analysis in several published gene expression datasets and a Fudan University cohort. Expression of immune cell populations and other immunotherapy predictors was further investigated. In TCGA LUAD cohort, eight B7-CD28 family genes had prognostic association with p values <0.05. Stepwise regression generated a gene signature including two genes, CD28 and CD276. Signature high-risk cases had worse overall survival (OS) and disease-free survival (DFS) in three published gene expression datasets and a Fudan University validation cohort. The B7-CD28 family based signature also significantly stratified OS and DFS in important clinical subsets, including stage I-II and EGFR mutant subsets. Signature high- and low-risk tumor had significantly different expressions of PD-L1 and tumor infiltrating leukocytes. The B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in LUAD. Whether it could serve as potential biomarkers for immunotherapy needs further investigation.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 69%

A B7‐CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma

Zheng

Luo

Dong

et al. 2018

Intl Journal of Cancer

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“…The serum levels of B7 family molecules, CD28, and VEGF were measured by using the following ELISA kits: human CD80 (CSB‐E15768h, Cusabio Biotech, Wuhan, China), human CD86 (CSB‐E08542h, Cusabio Biotech, Wuhan, China), human B7‐H4 (CSB‐E15013h, Cusabio Biotech, Wuhan, China), human PD‐1 (CSB‐E13643h, Cusabio Biotech, Wuhan, China), human PD‐L1 (CSB‐E13644h, Cusabio Biotech, Wuhan, China), human CD28 (CSB‐E09296h, Cusabio Biotech, Wuhan, China), human B7‐H3 (DB7H30, R&D Systems, Minneapolis, MN), human VEGF (DVE00, R&D Systems Minneapolis, MN), and human CTLA‐4 (KA0165, Abnova, Taipe, Taiwan), as described previously 16. The mean value for three blood samples was used.…”

Section: Methodsmentioning

confidence: 99%

“…In all analyses, a P value <0.05 was considered to indicate significance. Data were analyzed with commercially available software, as described previously 16.…”

Section: Methodsmentioning

confidence: 99%

Higher preoperative serum levels of PD‐L1 and B7‐H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF‐targeted therapy and unfavorable prognosis of renal cell carcinoma

et al. 2016

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Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer. Although antivascular endothelial growth factor (VEGF) therapies achieve impressive responses in some patients, many tumors eventually develop resistance to such therapy. The B7 family molecules such as CTLA‐4, PD‐1, and PD‐L1 are pivotal players in immune checkpoints that positively or negatively regulate various immune responses. Recently, immunotherapy based on blocking immune checkpoints with anti‐CTLA4, anti‐PD‐1, or anti‐PD‐L1 antibodies has been proposed as a potential new approach to the treatment of metastatic RCC. Higher expression of PD‐L1 and B7‐H4 in the tumors is associated with a poor prognosis in RCCs, however, the clinical impact of serum levels of B7 family molecules has not been elucidated in patients with metastatic RCCs receiving VEGF‐targeted agents. We assessed the preoperative serum levels of B7 family molecules, including CD80, CD86, PD‐1, PD‐L1, B7‐H3, B7‐H4, and CTLA‐4, and CD28 in RCC patients, and determined their relations with various clinicopathological characteristics. Elevated preoperative serum levels of PD‐L1 and B7‐H4 were correlated with less differentiated tumors, higher invasive and metastatic potential, a worse response to anti‐VEGF therapy, and shorter overall survival. These findings suggested that investigating preoperative serum levels of PD‐L1 and B7‐H4 might not only be useful to assess the biological aggressiveness of RCCs, but also to predict the efficacy of anti‐VEGF therapy and the eventual prognosis, indicating the future design of clinical trials of therapies targeting immune checkpoint in advanced RCCs.

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“…The duplication in 4IgB7-H3 generates a new conserved region in the first IgC domain, which might disable 4IgB7-H3 from releasing soluble form, while 2IgB7-H3 presents both membrane and soluble forms (14). Circulating serum B7-H3 levels are significantly higher in patients with lung cancer (15), colorectal carcinoma (CRC) (16), hepatocellular carcinoma (HCC) (17), renal cell carcinoma (RCC) (18) and glioma (19) than those in healthy volunteers.…”

Section: B7-h3mentioning

confidence: 99%

New B7 Family Checkpoints in Human Cancers

Dong

2017

Molecular Cancer Therapeutics

198

201

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T cells are the main effector cells in immune response against tumors. The activation of T cells is regulated by the innate immune system through positive and negative costimulatory molecules. Targeting immune checkpoint regulators such as programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has achieved notable benefit in a variety of cancers, which leads to multiple clinical trials with antibodies targeting the other related B7/CD28 family members. Recently five new B7 family ligands, B7-H3, B7-H4, B7-H5, B7-H6 and B7-H7, were identified. Here we review recent understanding of new B7 family checkpoint molecules since they have come to the front of cancer research with the concept that tumor cells exploit them to escape immune surveillance. The aim of this article is to address the structure and expression of the new B7 family molecules as well as their roles in controlling and suppressing immune responses of T cells as well as NK cells. We also discuss clinical significance and contribution of these checkpoint expressions in human cancers.

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Clinical Significance of Serum Soluble T Cell Regulatory Molecules in Clear Cell Renal Cell Carcinoma

Cited by 20 publications

References 36 publications

A B7‐CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma

A B7‐CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma

Higher preoperative serum levels of PD‐L1 and B7‐H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF‐targeted therapy and unfavorable prognosis of renal cell carcinoma

New B7 Family Checkpoints in Human Cancers

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