Soluble cytotoxic T-lymphocyte antigen 4: a favorable predictor in malignant tumors after therapy

Liu, Qiqi; Hu, Pingping; Deng, Guohua; Zhang, Jingxin; Liang, Ning; Xie, Jian; Qiao, Lili; Luo, Hui; Zhang, Jiandong

doi:10.2147/ott.s128451

Cited by 26 publications

(29 citation statements)

References 25 publications

(27 reference statements)

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“…In contrast, when serum levels of sCTLA‐4 were analyzed in patients with unresectable metastatic cancer or advanced lung or esophageal cancer, who have received at least one conventional first‐line therapy including radiotherapy or chemotherapy, it was found that sCTLA‐4 could be used as an important prognostic determinant. In fact, high expression of sCTLA‐4 significantly associated with longer overall survival or progression‐free survival . Similar observation of sCTLA‐4 overexpression in the serum or pleural effusion of pleural mesothelioma patients was observed, which indicated a favorable prognostic effect of the soluble isoform …”

Section: Immune Checkpoint Molecules: Regulating the Immune Responsesupporting

confidence: 69%

“…In fact, high expression of sCTLA-4 significantly associated with longer overall survival or progression-free survival. 43 Similar observation of sCTLA-4 overexpression in the serum or pleural effusion of pleural mesothelioma patients was observed, which indicated a favorable prognostic effect of the soluble isoform. 11…”

Section: Soluble Isoforms Of the Ctla-4/cd28:b7 Axissupporting

confidence: 63%

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Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

2019

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Background With the recent advances in the understanding of the interaction of the immune system with developing tumor, it has become imperative to consider the immunological parameters for both cancer diagnosis and disease prognosis. Additionally, in the era of emerging immunotherapeutic strategies in cancer, it is very important to follow the treatment outcome and also to predict the correct immunotherapeutic strategy in individual patients. There being enormous heterogeneity among tumors at different sites or between primary and metastatic tumors in the same individual, or interpatient heterogeneity, it is very important to study the tumor‐immune interaction in the tumor microenvironment and beyond. Importantly, molecular tools and markers identified for such studies must be suitable for monitoring in a noninvasive manner. Recent findings Recent studies have shown that the immune checkpoint molecules play a key role in the development and progression of tumors. In‐depth studies of these molecules have led to the development of most of the cancer immunotherapeutic reagents that are currently either in clinical use or under different phases of clinical trials. Interestingly, many of these cell surface molecules undergo alternative splicing to produce soluble isoforms, which can be tracked in the serum of patients. Conclusions Several studies demonstrate that the serum levels of these soluble isoforms could be used as noninvasive markers for cancer diagnosis and disease prognosis or to predict patient response to specific therapeutic strategies.

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Section: Immune Checkpoint Molecules: Regulating the Immune Responsesupporting

confidence: 69%

Section: Soluble Isoforms Of the Ctla-4/cd28:b7 Axissupporting

confidence: 63%

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

2019

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“…It was also suggested that high sCTLA‐4 levels affect the immunosuppressive function of regulatory T cells and support the response of effector T cells. Some of the data demonstrate that increased levels of CTLA‐4 after therapy are related with better overall survival rates; other data point out sCTLA‐4 serum levels as an independent prognostic factor in a variety of malignancies . Our results showed no significant difference in sCTLA‐4 serum levels before and after therapy.…”

Section: Clinical Parameters and Distribution Of Chl Patients At Diagcontrasting

confidence: 42%

“…Some of the data demonstrate that increased levels of CTLA-4 after therapy are related with better overall survival rates; other data point out sCTLA-4 serum levels as an independent prognostic factor in a variety of malignancies. 14 Our results showed no significant difference in sCTLA-4 serum levels before and after therapy. However, a minimal difference in sCTLA-4 serum levels at diagnosis was sufficient to reach correlation with a poor prognosis score (high IPS) in cHL patients.…”

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confidence: 49%

Soluble PD‐1 and PD‐L1 as potential biomarkers for classical Hodgkin lymphoma

Silva

Real

Ferreira

et al. 2018

Hematological Oncology

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“…A previous study also reported that decreases in serum IL-8 level 2-4 weeks after anti-PD-1 blockade therapies were strongly associated with response to immune checkpoint blockade in metastatic melanoma and NSCLC patients (24). Furthermore, higher serum TIM-3 or CD152 (also known as CTLA-4) level may indicate a more favorable clinical outcomes in advanced cancer patients, and higher baseline serum TIM-3 or CD152 can predict response to immune checkpoint blockade in patients with metastatic gastrointestinal tract cancer (15,25,26).…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Response to Combinational Use of PD-1 Blockade and Anti-angiogenesis: An Analysis from a Phase II Trial in Advanced Triple-negative Breast Cancer Patients

Liu

et al. 2020

Preprint

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Background: We recently reported the results of a phase II clinical trial that the combinational use of camrelizumab plus apatinib induced an objective response rate (ORR) at 43.3% in advanced triple-negative breast cancer (TNBC) patients. This study presents the analysis of potential tumor and blood biomarkers for the patients responded to the combinational therapy. Methods: Stromal tumor-infiltrating lymphocytes (TILs), CD8+ T cells and the protein expression of programmed death protein 1 (PD-1) and PD-L1 were evaluated in tumor samples collected before and after the treatment. Peripheral blood samples were collected before treatment, 2-weeks and 8-weeks after treatment. 59 cytokines/chemokines, growth factors, or checkpoint-related proteins, blood immune cell subpopulations were analyzed in the blood samples. The correlation between biomarkers and clinical outcomes including ORR, progression-free survival (PFS), and overall survival (OS) was analyzed. Results: Upon database lock, the ORR of 28 evaluable patients was 46.4%. An increase of tumor-infiltrating CD8+ T cells more than 15% during therapy was significantly associated with higher ORR (P=0.040). Patients with lower baseline plasma levels of HGF or IL-8 were more likely to respond to the combinational treatment (P=0.005 or 0.001, respectively), and showed a longer PFS and OS (HGF: PPFS<0.0001, POS<0.0001; IL-8: PPFS<0.0001, POS=0.009). Patients with a decrease of IL-8, or an increase of TIM-3 or CD152 during treatment responded more to the treatment (P=0.008, 0.040, or 0.014, respectively). Responders had a higher baseline CD4+ T cells and B cell proportions in blood than non-responders (P=0.002 and 0.030 respectively). Moreover, patients with higher baseline CD4+ T cells or B cells proportions in blood showed a longer PFS (P<0.001) or a longer OS (P=0.030) respectively. Conclusion: Higher baseline TILs or a greater increase of tumor-infiltrating CD8+ T cells during therapy, lower baseline plasma HGF/IL-8, a decrease of plasma IL-8, an increase of plasma TIM-3/CD152 during therapy, higher baseline CD4+ T cells or B cells proportion in blood are potential biomarkers for the combinational anti-angiogenesis and immunotherapy in advanced TNBC patients.

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Soluble cytotoxic T-lymphocyte antigen 4: a favorable predictor in malignant tumors after therapy

Cited by 26 publications

References 25 publications

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

Soluble PD‐1 and PD‐L1 as potential biomarkers for classical Hodgkin lymphoma

Biomarkers of Response to Combinational Use of PD-1 Blockade and Anti-angiogenesis: An Analysis from a Phase II Trial in Advanced Triple-negative Breast Cancer Patients

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