Search results for "pd-l1"

Through Predictive Personalized Medicine.

2020

Neuroblastoma (NBM) is a deadly form of solid tumor mostly observed in the pediatric age. Although survival rates largely differ depending on host factors and tumor-related features, treatment for clinically aggressive forms of NBM remains challenging. Scientific advances are paving the way to improved and safer therapeutic protocols, and immunotherapy is quickly rising as a promising treatment that is potentially safer and complementary to traditionally adopted surgical procedures, chemotherapy and radiotherapy. Improving therapeutic outcomes requires new approaches to be explored and validated. In-silico predictive models based on analysis of a plethora of data have been proposed by Lomba…

A pan-cancer analysis shows immunoevasive characteristics in NRF2 hyperactive squamous malignancies

2023

The NRF2 pathway is frequently activated in various cancer types, yet a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and utilized it to conduct a pan-cancer analysis of oncogenic NRF2 signaling. We identified an immunoevasive phenotype where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression and T cell and macrophage infiltration in squamous malignancies of the lung, head and neck area, cervix and esophagus. Squamous NRF2 overactive tumors comprise a molecular phenotype with SOX2/TP63 amplification, TP53 mutation and CDKN2A loss. These immune cold NRF2 hyperactive diseases are a…

P33.15 TMB in the First-Line Setting of NSCLC: A Systematic Review with Indirect Comparisons Between PD-1 and PD-L1 Inhibitors

2021

P37 Phase 1 evaluation of bintrafusp alfa (M7824), a bifunctional fusion protein targeting TGF-β and PD-L1, in cervical cancer

2019

Introduction/Background Globally, cervical cancer is one of the most common and lethal gynaecological cancers. Advanced/metastatic disease is typically treated with chemotherapy, often with poor objective response rates (ORRs) and durations of response (DORs) in pretreated patients; ORRs with anti-PD-1 therapies range from 12%-26%. Bintrafusp alfa* (M7824) is an innovative first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking PD-L1. We report safety and efficacy in patients with cervical cancer treated with bintrafusp alfa in dose-escalation and expansion phases of an ongoing phase 1 trial…

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4…

2021

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), a…

Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?

2022

Alterations in short-repetitive DNA sequences, known as microsatellite instability (MSI), can reflect deficiencies in Mismatch Repair (MMR) system which represents a major player in DNA integrity maintenance. The incidence of MSI-H/dMMR has been shown to be variable depending on the tumor type. Several studies confirmed that dMMR/MSI status, although less frequent than PD-L1 expression, may better predict response to immune-checkpoint inhibitors (ICIs) in patients with solid tumors. In October 2016, the FDA granted pembrolizumab as breakthrough therapy for the treatment of non-CRC, MSI-H/dMMR tumors, providing, for the first time, a tumor-agnostic indication. In the next future, the tissue-…

COLON CANCER CELL-DERIVED EXOSOMES INDUCE MACROPHAGES TO ACQUIRE AN IMMUNOSUPPRESSIVE PHENOTYPE BY UPREGULATING PD-L1 EXPRESSION

Tumor-associated macrophages (TAMs) are a prominent component of cancer microenvironment having a key role in promoting tumor progression. Several studies have demonstrated that TAMs phenotypically and functionally correspond to M2-polarized macrophages thus they exert immunosuppressive functions also associated to the expression of programmed cell death ligand 1 (PD-L1). Within the local tumor microenvironment, tumor-derived exosomes (TDEs) are well known to play a key role in modulating the properties and the behavior of surrounding cells such as TAMs. Even if several studies demonstrated the ability of TDEs to induce M2-like macrophage polarization, few data are available about their inv…

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

2020

The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in re…

Proceedings of Réanimation 2017, the French Intensive Care Society International Congress

2017

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

2017

IF 7.719; International audience; Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients. ACT may be optionally associated with chemo- and/or immunotherapeutics, with th…