Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients

Omura, Yusuke; Toiyama, Yuji; Okugawa, Yoshinaga; Yin, Chengzeng; Shigemori, Tsunehiko; Kusunoki, Kurando; Kusunoki, Yukina; Ide, Shozo; Shimura, Takaya; Fujikawa, Hiroyuki; Yasuda, Hiromi; Hiro, Junichiro; Ohi, Masaki; Kusunoki, Masato

doi:10.1007/s00262-020-02645-1

Cited by 42 publications

(45 citation statements)

References 43 publications

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“…In the present review, we provide evidence in support of this perspective. The number of CD8-positive T cells was significantly reduced in the tumor microenvironment of colorectal cancer tissues presenting CTLA-4 high expression [75] , consistent with the immunosuppressive effect of CTLA-4. Therefore, CTLA-4 has been developed as a new target for immunotherapy, and anti-CTLA-4 monoclonal antibodies could effectively induce antibody-dependent cell-mediated cytotoxicity (ADCC) of T cells [76] .…”

Section: Alternative Splicing Promotes Tumor Resistance To Immune Chesupporting

confidence: 67%

“…Although the immunosuppressive effect of mCTLA-4 and sCTLA-4 has been confirmed, its association with cancer prognosis remains controversial. To date, it has been revealed that the expression levels of mCTLA-4 and sCTLA-4 on tumors can be positively correlated with survival in esophageal and non-small cell lung cancer [ 72 , 73 ] and negatively correlated with prognosis in nasopharyngeal and colorectal cancer [ 74 , 75 ]. In the present review, we provide evidence in support of this perspective.…”

Section: Alternative Splicing Promotes Tumor Resistance To Immune Chementioning

confidence: 99%

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Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy

Deng

Jian

Huang

et al. 2021

Translational Oncology

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Highlights Abnormal alternative splicing is involve in abnormal expression of genes in cancer. Abnormal alternative splicing events promote malignant progression of cancer. Abnormal alternative splicing develops tumor resistance to targeted therapy by changing the target point and signal transduction pathway. Abnormal alternative splicing develops tumor resistance to immunotherapy by changing cell surface antigens and protein structure.

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Section: Alternative Splicing Promotes Tumor Resistance To Immune Chesupporting

confidence: 67%

Section: Alternative Splicing Promotes Tumor Resistance To Immune Chementioning

confidence: 99%

Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy

Deng

Jian

Huang

et al. 2021

Translational Oncology

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“…However, inhibiting tumoral CTLA-4 has resulted in PD-L1 upregulation and tumor relapse [ 13 , 14 ]. Omura et al have shown that the overexpression of membrane-bound CTLA-4 and membrane-bound PD-L1 in CRC cells can be associated with worse overall survival and disease-free survival (HR = 3.86, 95%, CI: 1.71–8.51, p -value = 0.001, and HR = 2.53, 95%, CI: 1.23–4.95, p -value = 0.01, respectively) [ 15 ]. Although our bioinformatic results have shown that CTLA-4 can be overexpressed in CRC tissues compared to the non-tumoral adjacent tissues, our clinical samples have failed to show any statistically significant differences between CRC tissues and adjacent non-tumoral tissues, which might be stemmed from our low sample size ( p -value > 0.05).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic T-Lymphocyte Antigen-4 in Colorectal Cancer: Another Therapeutic Side of Capecitabine

Derakhshani

Hashemzadeh

Asadzadeh

et al. 2021

Cancers

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Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can substantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy.

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“…Finally, 31 studies involving 17 tumors and a total of 3,780 patients met our inclusion criteria ( Figure 1 ). The tumor types included in the study were; Nasopharyngeal Carcinoma ( 11 ), Cholangiocarcinoma ( 12 ), lung cancer ( 9 , 10 , 13 – 17 ), Hepatocellular carcinoma ( 20 , 21 , 39 , 40 ), Thyroid carcinoma ( 22 ), Mesothelioma ( 23 ), Colorectal carcinoma ( 24 , 25 ), NK/T cell lymphoma ( 26 , 27 ), Peripheral T-cell lymphoma ( 28 ), Large B-Cell lymphoma ( 29 , 35 ), Hodgkin lymphoma ( 31 ), Ovarian carcinoma ( 32 ), Soft tissue sarcomas ( 33 ), Renal cell carcinoma ( 7 ), Esophageal carcinoma ( 34 ), Gastric carcinoma ( 4 , 35 ), and Pancreatic adenocarcinoma ( 36 , 41 ).…”

Section: Resultsmentioning

confidence: 99%

“…sPD-L1 can be used as a good indicator for the survival of cancer patients. Several studies have evaluated the predictive role of other immune-related biomarkers (such as soluble PD-L1, Vascular Endothelial Growth Factor A, soluble CD40L, CTLA-4, and soluble CD44) in different types of cancers ( 47 ). Meyo et al.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Circulating Soluble Programmed Death Ligand-1 in Cancers: A Meta-Analysis

Huang

Zhu

et al. 2021

Front. Oncol.

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BackgroundStudies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results.ObjectiveThis meta-analysis was performed to assess the association between sPD-L1 and the prognosis of cancer patients.MethodsPublished articles in Pubmed, EMBASE, and Cochrane clinical trial databases were searched from the inception to September 2020. Overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) data were evaluated using a hazard ratio (HR) at 95% confidence interval (95% CI).ResultsA total 31 studies involving 17 tumors and 3,780 patients were included. The overexpression of sPD-L1 was associated with shorter OS (HR 1.85, 95% CI 1.59–2.15, I2 = 33%). High sPD-L1 had worse PFS (HR 2.40, 95% CI 1.55–3.72, I2 = 83%), and worse DFS (HR 2.92, 95% CI 2.02–4.29, I2 = 40%), without significant statistical difference in RFS (HR 2.08, 95% CI 0.99–4.40, I2 = 0%).ConclusionsHigh sPD-L1 levels were associated with worse survival prognosis in cancer patients. The sPD-L1 may be a potential prognostic, non-invasive, and dynamic monitoring biomarker for cancers in the future.

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Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients

Cited by 42 publications

References 43 publications

Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy

Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy

Cytotoxic T-Lymphocyte Antigen-4 in Colorectal Cancer: Another Therapeutic Side of Capecitabine

The Prognostic Value of Circulating Soluble Programmed Death Ligand-1 in Cancers: A Meta-Analysis

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