In this issue of Cancer Cell, Patil et al. report that increased plasma cell signatures are predictive of an extended overall survival in non-small-cell lung cancer patients treated with a PD-L1 inhibitor and that these cells are associated with the presence of tertiary lymphoid structures.
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| http://dx.doi.org/10.1016/j.ccell.2022.02.008 | DOI Listing |
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Transient lymphocyte count decrease correlates with oncolytic adenovirus efficacy in humans: mechanistic and biomarker findings from TUNIMO phase I trial.
J Immunother Cancer
January 2025
Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
Article Synopsis
- TILT-123, an oncolytic virus engineered to enhance T-cell responses, was tested in the TUNIMO trial on 20 patients with advanced solid tumors to evaluate its safety, efficacy, and immunological effects.
- The study found that a greater decrease in blood lymphocyte count after treatment was associated with better tumor response and longer overall survival, which was corroborated by an external dataset of 96 patients.
- Analysis of tumor biopsies revealed an increase in immune cells, specifically CD8+ T cells, CD4+ T cells, and NK cells, suggesting that TILT-123 activates the immune response effectively in patients.
Intratumoral delivery of Mitomycin C using bio-responsive Gellan Gum Nanogel: In-vitro evaluation and enhanced chemotherapeutic efficacy.
Int J Biol Macromol
January 2025
Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
Intratumoral drug delivery systems hold immense promise in overcoming the limitations of conventional IV chemotherapy, particularly in enhancing therapeutic efficacy and minimizing systemic side effects. In this study, we introduce a novel redox-responsive intratumoral nanogel system that combines the biocompatibility of natural polysaccharides with the tailored properties of synthetic polymers. The nanogel features a unique cross-linked architecture incorporating redox-sensitive segments, designed to leverage the elevated glutathione levels in the tumor microenvironment for controlled drug release.
View Article and Find Full Text PDFPhase I study of adavosertib with radiation therapy and temozolomide in newly diagnosed glioblastoma and intratumoral drug levels in recurrent glioblastoma.
Clin Cancer Res
January 2025
Dana-Farber Cancer Institute, Boston, MA, United States.
Purpose: Adavosertib is an oral small molecular inhibitor of Wee1. The Adult Brain Tumor Consortium performed a phase I study of adavosertib, radiation (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) as well as a surgical window of opportunity study in recurrent GBM.
Patients And Methods: The maximum tolerated dose (MTD) of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in 2 separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ.
Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation.
Theranostics
January 2025
Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies. Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences. In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain.
View Article and Find Full Text PDFZinc nanoparticles from oral supplements accumulate in renal tumours and stimulate antitumour immune responses.
Nat Mater
January 2025
Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
A successful therapeutic outcome in the treatment of solid tumours requires efficient intratumoural drug accumulation and retention. Here we demonstrate that zinc gluconate in oral supplements assembles with plasma proteins to form ZnO nanoparticles that selectively accumulate into papillary Caki-2 renal tumours and promote the recruitment of dendritic cells and cytotoxic CD8 T cells to tumour tissues. Renal tumour targeting is mediated by the preferential binding of zinc ions to metallothionein-1X proteins, which are constitutively overexpressed in Caki-2 renal tumour cells.
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