Programmed Death-Ligand 1 Expression in Muscle-Invasive Bladder Cancer Cystectomy Specimens and Lymph Node Metastasis: A Reliable Treatment Selection Biomarker?

Mukherji, Deborah; Jabbour, Mark N.; Saroufim, Maya; Temraz, Sally; Nasr, Rami; Charafeddine, Maya; Assi, Rita; Shamseddine, Ali; Tawil, Ayman

doi:10.1016/j.clgc.2015.12.002

Cited by 44 publications

(28 citation statements)

References 11 publications

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“…Although local immune status may be easily evaluable in primary tumors resected before recurrence, the primary tumor and metastatic/recurrent lesions may show differences in phenotype and tumor immune status. The heterogeneity of PD‐L1 status between the primary cancer lesion and metastatic lymph nodes has been reported in triple negative breast cancer, clear cell renal cancer and bladder cancer 38‐40 . In addition, the tumor tissue obtained from the previous surgical treatment for the primary site may be considered old in comparison with that obtained from the current profound recurrent lymph node.…”

Section: Discussionmentioning

confidence: 99%

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

et al. 2020

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The relationship between the local immune status and cancer metabolism regarding 18F‐FDG and 18F‐FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty‐one ESCC patients who underwent 18F‐FDG PET and 18F‐FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD‐1), CD8, Ki‐67, CD34, GLUT1 (18F‐FDG transporter) and LAT1 (18F‐FAMT transporter). ESCC specimens with high tumoral PD‐L1 and high CD8‐positive lymphocytes were considered to have “hot tumor immune status.” High PD‐L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8‐positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki‐67 labelling index (P = 0.009) and CD34‐positive vessel counts (P < 0.001). SUVmax of 18F‐FDG was significantly higher in high PD‐L1 cases than in low PD‐L1 cases (P = 0.009). SUVmax of 18F‐FAMT was significantly higher in high PD‐L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18F‐FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.

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Section: Discussionmentioning

confidence: 99%

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

et al. 2020

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“…This may suggest a similar or even synergistic involvement of these two cellular components (TCs and IECs) in downregulation of anti-tumor response through PD-L1. There is no clear consensus on that matter in literature [35,36] Gehan-Wilcoxon, p = 0.013 Figure 3. The survival probability 20 and 50 months after cystectomy for UBC was about two and a half times and twice higher, respectively, in patients with tumor PD-L1 expression Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Expression of PD-L1 in tumor and immune system cells affects the survival of patients with urinary bladder cancer

Matusiak¹,

Dzierżawski²,

Jóźwicki³

et al. 2019

Medical Research Journal

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Background: The prediction of tumor malignancy is still one of the most demanding diagnostic tasks in urinary bladder cancer because of its clinicopathological heterogeneity. The aim of this study was to evaluate the expression of PD-L1 in tumor cells (TCs) and immune effector cells (IECs) as well as the pattern of distribution of PD-L1+ IECs within the tumor (dispersed or aggregated) and their association with survival of patients with pT1-pT4 urinary bladder cancer. Materials and methods: 110 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Paraffin blocks most representative of the tumor were selected for H&E staining as well as immunostaining with the use of rabbit anti-PD-L1 (Ventana clone SP142, Roche). In each sample, the area of the tumor containing PD-L1+ IECs, as well as, the pattern of distribution (dispersed or aggregated) of PD-L1+ immune effector cells within the tumor were analyzed. In addition, the expression of PD-L1 in TCs was also assessed. Results: Patients had a shorter survival time in pT2-pT4 cases without TCs expressing PD-L1 (p = 0.007) and/or when PD-L1+ IECs displayed a predominantly dispersed pattern of distribution (p = 0.013). Conclusions: The expression of PD-L1 on TCs and IECs is a prognostic factor which allows for stratification of patient survival in UBC. The predominance of dispersed or aggregated pattern of distribution of PD-L1+ IECs in the tumor may be considered as a new prognostic factor in pT1-T4 UBC and indicate the functional status of the immune system.

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“…It has been proven that biomarkers expressed at different disease sites or periods of disease progression might not reflect the current immune-active microenvironment. For instance, programmed death ligand-1 (PD-L1), a novel biomarker in PCa, is discordantly expressed in metastatic sites and primary tumors 24,25. Therefore, we believe it is necessary to further evaluate the association between SPINK1 expression and clinical outcomes in metastatic patients, especially the expression of SPINK1 in the metastatic site or stage.…”

Section: Discussionmentioning

confidence: 99%

The association between SPINK1 and clinical outcomes in patients with prostate cancer: a systematic review and meta-analysis

Zhang¹,

Yin

Shen³

et al. 2017

OTT

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Evidence of the prognostic role of serine peptidase inhibitor Kazal type 1 (SPINK1) in prostate cancer (PCa) is controversial. The aim of this study was, therefore, to evaluate the association between SPINK1 and clinical outcomes in PCa. Searches were made of PubMed, Medline, Embase, and the China Biology Medicine disc (CBMdisc) up to January 2017. The Newcastle–Ottawa Scale was used to assess the risk of bias of included studies. RevMan software was used to perform meta-analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was employed for assessing the quality of the evidence. Ten studies with 17,161 patients were included in the analysis. Random-effect models were adopted for all outcomes with significant heterogeneities. In patients treated with radical prostatectomy, SPINK1 was associated with biochemical recurrence (BCR) (hazard ratio [HR] =1.41, 95% confidence interval [CI]: 1.01–1.97; P=0.04), but not PCa-specific mortality (HR =0.93, 95% CI: 0.33–2.57; P=0.88), and overall survival (OS) (HR =0.89, 95% CI: 0.58–1.35; P=0.57). In metastatic PCa, SPINK1 was significantly associated with castration-resistant PCa-free survival (HR =3.87, 95% CI: 1.87–8.00; P=0.0003) and OS (HR =2.59, 95% CI: 1.16–5.78; P=0.02). However, the quality of the evidence was very low for all study outcome measures. In conclusion, although SPINK1 was not a predictor of PCa mortality or OS among patients who underwent radical prostatectomy, it may have prognostic value in metastatic PCa.

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Programmed Death-Ligand 1 Expression in Muscle-Invasive Bladder Cancer Cystectomy Specimens and Lymph Node Metastasis: A Reliable Treatment Selection Biomarker?

Cited by 44 publications

References 11 publications

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

Expression of PD-L1 in tumor and immune system cells affects the survival of patients with urinary bladder cancer

The association between SPINK1 and clinical outcomes in patients with prostate cancer: a systematic review and meta-analysis

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