PD-L1 Expression as a Predictive Biomarker in Advanced Non-Small-Cell Lung Cancer: Updated Survival Data

Aguiar, Pedro Nazareth; Mello, Ramon Andrade De; Hall, Peter; Tadokoro, Hakaru; Lopes, Gilberto

doi:10.2217/imt-2016-0150

Cited by 181 publications

(137 citation statements)

References 28 publications

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“…Targeting the PD-1/ PD-L1 pathway has shown encouraging results on various malignancies (9,(35)(36)(37) and has changed the standard of care in firstand second-line therapy of advanced NSCLC (5,6,(10)(11)(12). In this clinical setting, reliable predictive biomarkers are the object of significant financial investments although are difficult to obtain due to the complex tumor-host relationship.…”

Section: Discussionmentioning

confidence: 99%

“…Although the expression of PD-L1 by tumor cells potentially identifies NSCLC patients who would benefit from immune checkpoint inhibitors (ICI), it does not consistently represent a reproducible predictive biomarker of the clinical response (11)(12)(13). The attempt to correlate PD-L1 expression and patient prognosis has shown conflicting results (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

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Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value

Mazzaschi

Madeddu

Falco

et al. 2018

Clinical Cancer Research

191

148

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Purpose: The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially affect clinical outcome in nonsmall cell lung cancer (NSCLC), an extended analysis of PD-L1 and tumor-infiltrating lymphocytes (TIL) was performed.Experimental Design: Samples from resected adenocarcinoma (ADC 42), squamous cell carcinoma (SCC 58), and 26 advanced diseases (13 ADC and 13 SCC) treated with nivolumab were analyzed. PD-L1 expression and the incidence of CD3, CD8, CD4, PD-1, CD57, FOXP3, CD25, and Granzyme B TILs were immunohistochemically assessed.Results: PD-L1 levels inversely correlated with N involvement, although they did not show a statistically significant prognostic value in resected patients. The incidence and phenotype of TILs differed in SCC versus ADC, in which EGFR and KRAS mutations conditioned a different frequency and tissue localization of lymphocytes. NSCLC resected patients with high CD8 pos lymphocytes lacking PD-1 inhibitory receptor had a longer overall survival (OS: HR ¼ 2.268; 95% CI, 1.056-4.871, P ¼ 0.03). PD-1-to-CD8 ratio resulted in a prognostic factor both on univariate (HR ¼ 1.952; 95% CI, 1.34-3.12, P ¼ 0.001) and multivariate (HR ¼ 1.943; 95% CI, 1.38-2.86, P ¼ 0.009) analysis. Moreover, low PD-1 incidence among CD8 pos cells was a distinctive feature of nivolumab-treated patients, showing clinical benefit with a prolonged progressionfree survival (PFS: HR ¼ 4.51; 95% CI, 1.45-13.94, P ¼ 0.004).Conclusions: In the presence of intrinsic variability in PD-L1 expression, the reservoir of PD-1-negative effector T lymphocytes provides an immune-privileged microenvironment with a positive impact on survival of patients with resected disease and response to immunotherapy in advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value

Mazzaschi

Madeddu

Falco

et al. 2018

Clinical Cancer Research

191

148

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“…The most-studied biomarker to date is the PD-1 ligand, PD-L1; any expression of PD-L1 on tumour cells, and/or higher levels of tumour PD-L1 expression have both been associated with sensitivity to immune-checkpoint- inhibitor monotherapy in some tumour types, including melanoma and non-small-cell lung cancer (NSCLC), but with conflicting results in other diseases 160–162 . In studies of small numbers of cholangiocarcinoma tumour samples ( n = 54–99), PD-L1 expression has been reported in 9–72% of specimens 163–165 , and on 46–63% of immune cells within the tumour microenvironment 164,165 .…”

Section: Emerging Molecularly-directed Therapiesmentioning

confidence: 99%

Cholangiocarcinoma — evolving concepts and therapeutic strategies

et al. 2017

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Cholangiocarcinoma is a disease entity comprising diverse epithelial tumours with features of cholangiocyte differentiation: cholangiocarcinomas are categorized according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management. The incidence of cholangiocarcinoma, particularly iCCA, has increased globally over the past few decades. Surgical resection remains the mainstay of potentially curative treatment for all three disease subtypes, whereas liver transplantation after neoadjuvant chemoradiation is restricted to a subset of patients with early stage pCCA. For patients with advanced-stage or unresectable disease, locoregional and systemic chemotherapeutics are the primary treatment options. Improvements in external-beam radiation therapy have facilitated the treatment of cholangiocarcinoma. Moreover, advances in comprehensive whole-exome and transcriptome sequencing have defined the genetic landscape of each cholangiocarcinoma subtype. Accordingly, promising molecular targets for precision medicine have been identified, and are being evaluated in clinical trials, including those exploring immunotherapy. Biomarker-driven trials, in which patients are stratified according to anatomical cholangiocarcinoma subtype and genetic aberrations, will be essential in the development of targeted therapies. Targeting the rich tumour stroma of cholangiocarcinoma in conjunction with targeted therapies might also be useful. Herein, we review the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma.

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“…Özellikle hücre membranında ve sitoplazmasında eksprese olan PD-L1'in immünhistokimyasal yolla boyanarak saptanmasıyla immünoterapi için en uygun hasta adayları belirlenir. PD-L1 immünekspresyonu gösteren hastaların belirgin olarak immünterapötiklerden fayda gördüğü gösterilmiştir (53). Ticari olarak DAKO ve Ventana markaları altında yer alan beş adet PD-L1 immünhistokimya antikoru (22C3, 28-8, SP 142, SP 263 ve 73-10) ve platformunun her biri farklı bir immünoterapötik ajan (pembroluzimab, nivolumab, atezolizumab, durvalumab ve avelumab) için geliştirilmiş olup, her bir antikorun değerlendirmedeki sınır değerler ve yöntemleri (sadece tümör hücreleri veya tümör hücreleri ve tümörü infiltre eden immün hücreler) farklılık göstermektedir.…”

Section: İmmünoterapi (Pd1/pd-l1)unclassified

Molecular Pathology of Lung Cancer

Bozkurtlar¹,

Kaya²

2018

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PD-L1 Expression as a Predictive Biomarker in Advanced Non-Small-Cell Lung Cancer: Updated Survival Data

Abstract: PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

Cited by 181 publications

References 28 publications

Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value

Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value

Cholangiocarcinoma — evolving concepts and therapeutic strategies

Molecular Pathology of Lung Cancer

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