PD-L1 directed bispecific V{delta}2-T cell engager combines lysis of PD-L1 expressing tumor cells with PD-1 immune checkpoint inhibition and modulation of the tumor immune microenvironment

Background
Despite the notable success of programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1) immune checkpoint blockade in cancer, resistance remains a substantial challenge. Combining immune checkpoint blockade with direct targeting of effec…

Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic

Almost every successful anticancer treatment has been preceded by preclinical scientific breakthroughs that encouraged clinical development. However, therapeutic strategies showing promising preclinical results often fail to confirm activity in clinic…

Acetaminophen interactions with immune checkpoint inhibitors: guilt by association?

Recent studies suggest that acetaminophen may be linked to poorer long-term outcomes in patients receiving immune checkpoint inhibitors. Since acetaminophen is a widely used and essential medication for many patients with cancer, it is important to ca…

Metagenomic next-generation sequencing unraveled the characteristic of lung microbiota in patients with checkpoint inhibitor pneumonitis: results from a prospective cohort study

Background
Checkpoint inhibitor pneumonitis (CIP) is among the most lethal immune-related adverse events in patients with cancer receiving immunotherapy. This study aims to characterize the lung microbiome in patients with CIP and evaluate its diagnos…

Bi-specific T cell-engaging antibody triggers protective immune memory and glioma microenvironment remodeling in immune-competent preclinical models

Background
Bispecific T cell-engagers (BTEs) are engineered antibodies that redirect T cells to target antigen-expressing tumors. BTEs targeting tumor-specific antigens such as interleukin 13 receptor alpha 2 (IL13RA2) and epidermal growth factor rece…

Combination of a novel TCR V{beta} chain-directed selective T cell activator with standard of care therapy for head and neck cancer improves antitumor responses and promotes regression of checkpoint-refractory tumor models

Background
Immune checkpoint blockade (ICB) treatment, alone or in combination with standard anticancer therapies, has led to important progress in the treatment of head and neck squamous cell carcinoma (HNSCC). Yet, a significant proportion of patien…

Genetic haplotypes in VWA8, OSBPL6, and ADAMTS9-AS2 are associated with immune-related adverse effects in ICI-treated patients with cancer

Background
Immune-related adverse events (irAEs) remain largely unpredictable, potentially affecting multiple organ systems and occurring at almost any point during and even occasionally after immune checkpoint inhibitor (ICI) treatment. To identify p…

Targeting PD-L1-CMTM6 interactions in myeloid cells triggers PD-L1 degradation and enhances cytotoxic T-cell expansion

Background
Immune checkpoint therapies targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have been met with limited clinical responses in the treatment of patients of varying cancer types. Current US Food and Drug …

CPT1A inhibition alleviates plasmacytoid dendritic cell-mediated immune suppression in colon cancer through fatty acid oxidation modulation

Background
The tolerization of plasmacytoid dendritic cells (pDCs) within the tumor microenvironment facilitates immune evasion, thereby significantly limiting the efficacy of cancer immunotherapy. Metabolic regulators are crucial in determining immun…

CPT1A inhibition alleviates plasmacytoid dendritic cell-mediated immune suppression in colon cancer through fatty acid oxidation modulation

Background
The tolerization of plasmacytoid dendritic cells (pDCs) within the tumor microenvironment facilitates immune evasion, thereby significantly limiting the efficacy of cancer immunotherapy. Metabolic regulators are crucial in determining immun…

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