Search results for "immune checkpoint"

Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and patho…

2018

Background The molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors. Material and methods We collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation. Results Forty-five (18%) cas…

Prognostic role of immune checkpoint-related genes in resectable lung adenocarcinomas.

2014

11085 Background: Immune checkpoints blockade has demonstrated promising clinical results in NSCLC patients. In this study we have investigated the prognostic role of immune checkpoint markers (CTLA4, PD1 and PDL1) in resectable lung adenocarcinoma (ADC). Methods: RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) from resectable ADC patients (n=92). RT-PCR was performed to analyze the expression of CTLA4, PD1 and PDL1 by the use of hydrolysis probes. Relative gene expression was assessed by Pfaffl formula and normalized by CDKN1B and ACTB as endogenous genes (selected by geNorm algorithm). Statistical analyses were considered significant at p<0.05. Results: Patient’s…

Abstract 4330: Immune checkpoint expression score is an independent prognostic biomarker in resectable non-small cell lung cancer

2015

Abstract BACKGROUND Immune checkpoints blockade, which activate antitumor immunity, has demonstrated promising clinical results in NSCLC. In this study we have investigated the prognostic role of immune checkpoint expression markers and its correlation with immune-cells infiltration and clinico-pathological characteristics in a cohort of resectable NSCLC patients. MATERIAL AND METHODS RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the expression of CTLA-4, PD-1 and PD-L1 by the use of hydrolysis probes. Relative gene expression was assessed by Pfaffl formula and normalized by the use of CDKN1B, GUS and ACTB as endogenous …

In the literature: December 2018

2018

The current development of immune checkpoint modulatory treatments has shown durable responses in the treatment of multiple cancer types.1 However, predictive biomarkers beyond PD-1 ligand 1 (PD-L1) expression and high microsatellite instability (MSI-H) to stratify patients and identify those who could benefit of these therapies are needed. In this sense, a recent study published in Science by Cristescu et al 2 describes the potential usefulness of combining the tumour mutational burden (TMB) and the T cell-inflamed gene expression profile (GEP) to jointly predict clinical response to pembrolizumab. Both PD-L1 and the GEP represent a T cell-inflamed tumour microenvironment (TME), whereas TM…

Abstract 4082: Preclinical assessment of external or targeted radiotherapy in combination with immunotherapies and co-development of companion imagin…

2019

Abstract Immunotherapies have proven to be highly efficient for cancer treatments and combination with either internal vectorized or external radiotherapies can enhance this efficacy through notably increasing tumor immune infiltrate. The clinical evaluation of such combination therapies requires expertise and exquisite processes in multiple fields, immunotherapy, radiotherapy and nuclear medicine. Similarly, this applies into preclinical settings for assessing proof of concept of novel combinations. Herein, we will present our preclinical evaluation process to combine external or internal (i.e. lutetium-177 radiolabeled molecule) radiotherapy with immunotherapies that include radiochemistr…

116 Evaluation of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in cervical cancer: data from phase 1 and phase 2 studies

2021

Introduction/Background* The accelerated US Food and Drug Administration approval of pembrolizumab validated the efficacy of anti-PD-(L)1 therapy for patients with recurrent/metastatic cervical cancer; however, the objective response rate (ORR) with pembrolizumab was 14.3% in patients with PD-L1–expressing tumours. Human papillomavirus infection is implicated in >95% of cervical cancers and is linked to upregulation of TGF-β signalling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 monoclonal antibody blocking PD-L1. We report pooled safety and efficacy in pati…

Understanding mechanisms of primary resistance to checkpoint inhibitors will lead to precision immunotherapy of advanced gastric cancer

2019

PRODIGE 59-DURIGAST trial: A randomised phase II study evaluating FOLFIRI + Durvalumab ± Tremelimumab in second-line of patients with advanced gastri…

2021

International audience; Gastric or gastro-oesophageal junction (GEJ) adenocarcinomas present poor overall survival (OS). First-line chemotherapy regimen for patients with HER2-negative tumours is based on a doublet or triplet of fluoropyrimidine plus platinum salt ± taxane. Second-line chemotherapy (Docetaxel or Irinotecan) improves OS which nonetheless remains poor (around 5 months). The first results of immune checkpoint inhibitors (anti-PD-1) combined with chemotherapy in metastatic gastric and GEJ cancers were discordant in recent phase III trials. Data on dual-blockade (anti-PD-L1 or anti-PD-1 plus anti-CTLA-4) plus chemotherapy are lacking. DURIGAST is a randomised, multicenter, non-c…

A Systematic Review of the Emerging Role of Immune Checkpoint Inhibitors in Metastatic Castration-resistant Prostate Cancer: Will Combination Strateg…

2020

Abstract Context The role of immune checkpoint inhibition (ICI) in the treatment of prostate cancer (PC) still remains elusive. It has been proposed that combination of ICI with other molecules increases the efficacy of immunotherapy in PC. Objective To systematically review the literature to assess the potential role of ICI in combination with additional therapies for the management of metastatic castration-resistant PC (mCRPC). Evidence acquisition A systematic review using Medline and scientific meeting records was carried out in September 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. Ongoing trials of immunotherapy with standard mCRP…

Immunotherapeutic Advances for NSCLC.

2021

Abstract Immunotherapy with antibodies against PD-1 or PD-L1, either alone or in combination with chemotherapy, has revolutionized treatment paradigms of non-small cell lung cancer (NSCLC) patients without oncogenic driver alterations. These agents, namely immune checkpoint inhibitors (ICIs), have also widely demonstrated a remarkable efficacy in locally advanced as well as in early-stage NSCLC. Assessment of tumor PD-L1 expression by immunohistochemistry has entered into routine clinical practice to select patients for immunotherapy, even though its predictive role has long been debated. Despite improved survival outcomes over standard chemotherapy, treatment with ICIs is associated with i…