The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis

Aguiar, Pedro Nazareth; Santoro, Ilka Lopes; Tadokoro, Hakaru; Lopes, Gilberto; Filardi, Bruno Andraus; Oliveira, Pedro F.; Mountzios, Giannis; Mello, Ramon Andrade De

doi:10.2217/imt-2015-0002

Cited by 135 publications

(96 citation statements)

References 24 publications

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“…To be able to improve survival in lung cancer in general, the next step should be to focus on the treatment of those patients. Immunotherapy nowadays seems a step forward in reaching this goal [1].…”

Section: Change In the Insight Of Lung Cancermentioning

confidence: 99%

“…In recent years, changes at the "macroscopic level" are supplemented by the insight in the microscopic world of the lung cancer such as discovery of EGFR mutations and more and more important knowledge about complex immunologic interactions between tumors and the host environment [1].…”

Section: Change In the Insight Of Lung Cancermentioning

confidence: 99%

“…A higher number of mutations, commonly called mutation burden, is connected to higher immunogenicity of tumors. NSCLC and melanomas are cancers with the highest burden among several solid tumors and because of that they are believed to be good targets for immunotherapy [1]. The problem of immune recognition and cancer is that cancers have the ability to evade the immune system, and this is one of the hallmarks of cancer [5].…”

Section: Immune System and Cancermentioning

confidence: 99%

“…It is not related to treatment, but rather to tumor biology. It helps physicians and patients to predict the course of the disease [1,[13][14][15]. Before a marker is labelled predictive, the effect of a marker as a prognostic marker must be taken into account [16].…”

Section: Why Do We Need Prognostic and Predictive Biomarkersmentioning

confidence: 99%

“…Prognostic biomarkers provide information about the patient's overall cancer outcome, regardless of the therapy. Predictive biomarkers give information about the effect of a therapeutic intervention [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic and Predictive Value of PD-L1 in Patients with Lung Cancer

Rajer¹

2017

A Global Scientific Vision - Prevention, Diagnosis, and Treatment of Lung Cancer

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Improved understanding of the molecular mechanisms has led to identification of checkpoint signalling and development of checkpoint inhibitors in the treatment of many cancers, including lung cancer. To be able to select the patients who benefit most from checkpoint inhibitors, predictive biomarkers are needed. Currently, the only predictive biomarker that has been approved in clinical use is PD-L1, the ligand of the inhibitory T-cell checkpoint PD-1. The use of PD-L1 as a predictive biomarker is confounded by multiple unresolved issues, from testing issues (e.g., cut-off values for positivity) to clinical use (e.g., the response to anti-PD-1 and anti-PD-L1 antibodies in patients without any expression of PD-L1). Even more open questions exist in the evaluation of PD-L1 as a prognostic biomarker. In the future, we expect that an improved understanding of immune system, tumor microenvironment, mechanism of action of immunotherapeutic drugs, and PD-L1 testing methods will elucidate the value of PD-L1 as a prognostic and predictive biomarker in detail.

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Section: Change In the Insight Of Lung Cancermentioning

confidence: 99%

Section: Change In the Insight Of Lung Cancermentioning

confidence: 99%

Section: Immune System and Cancermentioning

confidence: 99%

Section: Why Do We Need Prognostic and Predictive Biomarkersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic and Predictive Value of PD-L1 in Patients with Lung Cancer

Rajer¹

2017

A Global Scientific Vision - Prevention, Diagnosis, and Treatment of Lung Cancer

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Soluble galectin‐3 as a microenvironment‐relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma

Torres‐Martínez,

Calabuig‐Fariñas,

Moreno‐Manuel

et al. 2023

Molecular Oncology

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Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin‐3 (GAL‐3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non‐small cell lung cancer (NSCLC) patients. For in vitro studies, lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) primary cultures from early‐stage patients and commercial cell lines were cultured, using tumorsphere‐forming assays and adherent conditions for the control counterparts. We analyzed the pattern of secretion and expression of GAL‐3 using reverse transcription–quantitative real‐time PCR (RTqPCR), immunoblot, immunofluorescence, flow cytometry and immunoassay analysis. Our results using three‐dimensional (3D) models of lung tumor cells revealed that soluble GAL‐3 (sGAL‐3) is highly expressed and secreted. To more accurately mimic the TME, a co‐culture of tumorspheres and fibroblasts was used, revealing that GAL‐3 could be important as an immunomodulatory molecule expressed and secreted in the TME, modulating immunosuppression through regulatory T cells (TREGS). In the translational phase, we confirmed that patients with high expression levels of GAL‐3 had more TREGS, which suggests that tumors may be recruiting this population through GAL‐3. Next, we evaluated levels of sGAL‐3 before surgery in LUAD and LUSC patients, hypothesizing that sGAL‐3 could be used as an independent prognostic biomarker for overall survival and relapse‐free survival in early‐stage LUAD patients. Additionally, levels of sGAL‐3 at pretreatment and first response assessment from plasma to predict clinical outcomes in advanced LUAD and LUSC patients treated with first‐line pembrolizumab were evaluated, further supporting that sGAL‐3 has a high efficiency in predicting durable clinical response to pembrolizumab with an area under curve (AUC) of 0.801 (p=0.011). Moreover, high levels might predict decreased progression‐free survival and overall survival to anti‐PD‐1 therapy, with sGAL‐3 being a prognosis‐independent biomarker for advanced LUAD.

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Biomarkers from Bench to Bedside and Back – Back‐Translation of Clinical Studies to Preclinical Models

O’Connell

Shaikhibrahim

Ocker

2020

Biomarkers in Drug Discovery and Development

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The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis

Abstract: Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment.

Cited by 135 publications

References 24 publications

Prognostic and Predictive Value of PD-L1 in Patients with Lung Cancer

Prognostic and Predictive Value of PD-L1 in Patients with Lung Cancer

Soluble galectin‐3 as a microenvironment‐relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma

Biomarkers from Bench to Bedside and Back – Back‐Translation of Clinical Studies to Preclinical Models

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