Expression of PDL1 (B7-H1) Before and After Neoadjuvant Chemotherapy in Urothelial Carcinoma

McDaniel, Andrew S.; Alva, Ajjai; Zhan, Tianyu; Xiao, Hong; Cao, Xuhong; Gursky, Amy; Siddiqui, Javed; Chinnaiyan, Arul M.; Jiang, Hui; Lee, Cheryl T.; Mehra, Rohit

doi:10.1016/j.euf.2015.03.004

Cited by 50 publications

(38 citation statements)

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“…The differences observed in the positivity rate of PD-L1 in ESCC may be attributed to the antibodies used in the IHC staining and the scoring criteria for the staining. The positivity rate of PD-L1 is also dependent on whether the patients received any treatment before sample collection since chemotherapy and radiotherapy induce PD-L1 expression, as demonstrated by our current study and other reports [8], [26], [27]. Previous studies demonstrate that high PD-L1 expression is associated with advanced disease and lymph node metastasis in various cancers [28], [29], [30].…”

Section: Discussionsupporting

confidence: 80%

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Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation

Tao

et al. 2018

Translational Oncology

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The current study reveals the clinicopathological association of PD-L1 in Hong Kong esophageal squamous cell carcinoma (ESCC) patients and the differential regulation of PD-L1 by standard first-line chemotherapy in ESCC. Immunohistochemical analysis of tissue microarray data from 84 Hong Kong ESCC patients shows that PD-L1 was expressed in 21% of the tumors. Positive PD-L1 staining was significantly associated with later disease stage (stages III and IV) (P value = .0379) and lymph node metastasis (P value = .0466) in the Hong Kong cohort. Furthermore, PD-L1 expression was significantly induced in ESCC cell lines after standard chemotherapy treatments, along with EGFR and ERK activation in both in vitro studies and the in vivo esophageal orthotopic model. The endogenous expression of PD-L1 was reduced by treatment with an EGFR inhibitor (erlotinib) or by the knockdown of EGFR. Moreover, the upregulation of PD-L1 by chemotherapy was also attenuated by the treatment with erlotinib and a MAPK/MEK inhibitor (AZD6244), suggesting that PD-L1 is regulated by the EGFR/ERK pathway in ESCC. The regulation of PD-L1 by the EGFR pathway was further supported by the correlation of PD-L1 and EGFR expression observed in the commercially available tissue microarray set (P value = .028). Taken together, the current study was the first to demonstrate the upregulation of PD-L1 by chemotherapy in ESCC and its regulation through the EGFR/ERK pathway. The results suggest the potential usefulness of combined conventional chemotherapy together with anti–PD-L1 immunotherapy to achieve better treatment outcome.

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Section: Discussionsupporting

confidence: 80%

“…For example, it is demonstrated that PD-L1 expression increased after the treatment with cisplatin/carboplatin in urothelial carcinoma [8]. Also, paclitaxel induced PD-L1 in the human colon adenocarcinoma cell line SW480 and the hepatocellular carcinoma cell line HepG2 [9].…”

Section: Introductionmentioning

confidence: 99%

Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation

Tao

et al. 2018

Translational Oncology

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“…In particular, it has recently been shown that PD‐L1 significantly increased on residual disease after NACT compared with baseline in a large retrospective cohort of patients with TN early BC . The induction of PD‐L1 expression by chemotherapy is consistent with observations in other cancer types and with the notion that chemotherapy is able to induce an adaptive immune response through various mechanisms, including immunogenic cell death and the activation of the damage response c‐GAS/STING . Indeed, it has been shown that CT may boost the immunogenicity of the tumor by increasing tumor immune infiltrate from baseline to post‐NACT samples, with a high rate of conversion from low‐TIL to high‐TILs tumor .…”

Section: Methodssupporting

confidence: 71%

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. Implications for Practice In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.

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“…Chemotherapy may be acting as an immunomodulator that increases PD-L1 expression in tumor immune-infiltrating cells. This was demonstrated in a retrospective analysis by IHC staining for PD-L1 in matched samples from 40 patients with MIBC before and after neoadjuvant chemotherapy [42]. The study showed that PD-L1 tumor expression was significantly higher after neoadjuvant chemotherapy compared with baseline ( P = 0.0235), indicating that adaptive regulation of the immune response by PD-L1 can occur in patients with MIBC treated with neoadjuvant chemotherapy.…”

Section: New Immune Targetsmentioning

confidence: 84%

Immunotherapy: a new treatment paradigm in bladder cancer

Davarpanah

Yuno

Trepel

et al. 2017

Current Opinion in Oncology

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Purpose of reviewT-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy.Recent findingsProgramed cell death protein 1/programed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors have achieved durable clinical responses in a subset of previously treated and treatment-naïve patients with mUC. The combination of PD-1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) has successfully improved response rates in multiple malignancies, and combination studies are underway in many tumor types, including bladder cancer, combining T-cell checkpoint blockade with other checkpoint agents and immunomodulatory therapies. Strong tumor responses to checkpoint blockade have been reported to be positively associated with expression of PD-L1 on tumor and tumor-infiltrating immune cells and with increased mutation-associated neoantigen load, which may lead to the development of predictive biomarkers.SummaryRecent clinical evidence suggests that mUC is susceptible to T-cell checkpoint blockade. A global effort is underway to achieve higher response rates and more durable remissions, accelerate the development of immunotherapies, employ combination therapies, and test novel immune targets.

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Expression of PDL1 (B7-H1) Before and After Neoadjuvant Chemotherapy in Urothelial Carcinoma

Cited by 50 publications

References 10 publications

Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation

Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Immunotherapy: a new treatment paradigm in bladder cancer

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