Soluble programmed death-ligand 1 rather than PD-L1 on tumor cells effectively predicts metastasis and prognosis in soft tissue sarcomas

Asanuma, Kunihiro; Nakamura, Tomoki; Hayashi, Akiko; Okamoto, Takayuki; Iino, Takahiro; Asanuma, Yumiko; Hagi, Tomohito; Kita, Kouji; Nakamura, Kouichi; Sudo, Akihiro

doi:10.1038/s41598-020-65895-0

Cited by 43 publications

(37 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data showed that 19 of 21 cervical cancer patients had sPD‐L1 levels above the mean of the controls. sPD‐L1 levels have been increased in different types of cancer and are associated with disease severity and prognosis [13,60,61]. It is also possible that the presence of sPD‐L1 may indicate patients who would not respond well to some forms of PD‐L1 blockade antibody therapy, as it has been reported that secreted PD‐L1 variants can mediate resistance to PD‐L1 blockade by acting as a decoy [10].…”

Section: Discussionmentioning

confidence: 99%

“…The over‐expression of PD‐L1 in tumor tissues has been considered as a predictive biomarker; however, some authors have concluded that this molecule may not be a robust indicator of treatment response due to the fact that PD‐L1‐negative tumors can also respond to PD‐1/PD‐L1 targeting [11,12]. The soluble form of PD‐L1 (sPD‐L1) has been reported to be an improved predictor of metastasis versus membrane‐bound PD‐L1 and a prognostic factor for the survival of first‐line chemotherapy, and may also mediate resistance to PD‐L1 blockade [13‐16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis

Solorzano‐Ibarra

Alejandre-Gonzalez

Ortiz‐Lazareno

et al. 2021

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti‐programmed cell death 1 (PD‐1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine‐based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim‐3 and PD‐1 on subsets of peripheral blood NK (CD56dim/negCD16bright/dim/neg and CD56brightCD16dim/neg) and T cells. The percentages of these cells were increased in women with cervical cancer and pre‐malignant lesions. PD‐1+ NK and T cells were likely to co‐express TIGIT and/or Tim‐3. These cells, with an apparently ‘exhausted’ phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)‐ and DNAX accessory molecule 1 (DNAM‐1)‐positive. PD‐1int and PD‐1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD‐L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD‐L1 and PD‐1+ T cells in women with low‐grade lesions. Within the cancer group, there were no significant correlations between sPD‐L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD‐L1 and total T cells and a correlation between sPD‐L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre‐cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis

Solorzano‐Ibarra

Alejandre-Gonzalez

Ortiz‐Lazareno

et al. 2021

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…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%

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

Huang

Zhu

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

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.

show abstract

“…In gastric cancer, although serum sPD-L1 levels showed a trend of elevation in patients with high tissue PD-L1 expression, a statistically significance was not observed ( 20 ). A recent study performed in soft tissue sarcomas also revealed that there were no obvious differences in sPD-L1 levels between tissue PD-L1 positive group and PD-L1 negative group ( 35 ). One possible explanation is the mPD-L1 expression may vary within the same tumor spatially and temporally.…”

Section: Discussionmentioning

confidence: 96%

Soluble PD-L1 as a Predictor of the Response to EGFR-TKIs in Non-small Cell Lung Cancer Patients With EGFR Mutations

Jia

Zhao

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Programmed cell death ligand 1 (PD-L1) expressed on tumor tissues is a vital molecule for immune suppression and its impact on the response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been reported. The significance of soluble PD-L1 (sPD-L1) for lung cancer patients remains unknown. This study investigated whether sPD-L1 could predict the response of EGFR-mutated non-small cell lung cancer (NSCLC) to EGFR-targeted therapy. We retrospectively evaluated patients who received first-line treatment with EGFR-TKIs for advanced NSCLC with EGFR mutations. Pre-treatment plasma concentrations of PD-L1 and on-treatment (1 month after treatment initiation) plasma concentrations of PD-L1 were measured using the R-plex Human PD-L1 assay. The association between the sPD-L1 level and the clinical outcome was analyzed. Among 66 patients who were eligible for the study, patients with high pre-treatment or on-treatment sPD-L1 levels had decreased objective response rate (ORR) compared with that of patients with low sPD-L1 levels (39.4 vs. 66.7%, p = 0.026 for pre-treatment sPD-L1 level, and 43.5 vs. 73.9%, p = 0.025 for on-treatment sPD-L1 level). A high baseline sPD-L1 level was associated with a shortened progression-free survival (PFS) rate (9.9 vs. 16.1 months, p = 0.005). Both univariate and multivariate analyses showed that a high baseline sPD-L1 level was an independent factor associated with the PFS (hazard ratio [HR] 2.56, p = 0.011). Our study revealed that the sPD-L1 level was strongly related to the outcome of EGFR-TKIs in NSCLC patients harboring EGFR mutations.

show abstract

Soluble programmed death-ligand 1 rather than PD-L1 on tumor cells effectively predicts metastasis and prognosis in soft tissue sarcomas

Cited by 43 publications

References 47 publications

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis

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

Soluble PD-L1 as a Predictor of the Response to EGFR-TKIs in Non-small Cell Lung Cancer Patients With EGFR Mutations

Contact Info

Product

Resources

About