Decoding neoantigen-encoding tumor-specific transcripts unveils a shared target reservoir for immunotherapy in hepatocellular carcinoma

Background
Primary liver cancer, predominantly hepatocellular carcinoma (HCC), has limited therapeutic options. While mutation-derived neoantigen vaccine holds promise, its success is hindered by low antigen availability. This study explores transcrip…

Intratumoral Capnocytophaga leadbetteri promotes cancer cells proliferation and recruits neutrophils by activating TLR4/MyD88/NF-{kappa}B axis in oral squamous cell carcinoma

Background
Intratumoral bacteria influence the progression and treatment response of solid tumors through multiple mechanisms. Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck; however, the role of intratumoral bact…

Safety and efficacy of fecal microbiota transplantation in solid cancers resistant to immune checkpoint inhibitors: results of the MITRIC trial

Background
Fecal microbiota transplantation (FMT) has shown promise in overcoming resistance to immune checkpoint inhibitors (ICIs) in early-phase cancer trials. We investigated the safety, feasibility and efficacy of FMT from ICI responders to patien…

Phase 1/2 study of IMC-C103C, a T cell receptor bispecific (MAGE-A4xCD3) ImmTAC targeting MAGE-A4-expressing malignancies

Purpose
IMC-C103C is an ImmTAC bispecific (MAGE-A4xCD3) T cell engager targeting a peptide from the cancer-testis antigen MAGE-A4 presented by HLA-A*02:01. This phase 1/2 study in advanced solid tumors (IMC-C103C-101; NCT03973333) investigated the saf…

Frontline immunotherapy with response-guided subsequent treatment (FIRST) in cutaneous squamous cell carcinoma: a Bayesian causal analysis of dose intensity, early benefit, and treatment de-escalation

Background
Programmed death receptor 1 (PD-1) blockade produces high response rates in resectable and locally advanced cutaneous squamous cell carcinoma (CSCC), but how many doses are needed and whether surgery or radiation after immunotherapy (consol…

Spatial architecture of tertiary lymphoid structures represents an independent prognostic dimension in hepatocellular carcinoma

Background and aims
Tertiary lymphoid structures (TLS) are associated with heterogeneous outcomes in hepatocellular carcinoma (HCC), but whether their anatomical context determines clinical impact remains unknown. We hypothesized that spatial compartm…

Blautia coccoides-derived acetate potentiates anti-PD-1 immunotherapy in melanoma by activating cytotoxic CD8+ T cells

Background
Gut microbiota can modulate cancer immunotherapy and enhance the efficacy of programmed cell death protein 1 (PD-1) blockade in tumors, yet the responsible microbes and underlying mechanisms remain incompletely understood.

Methods
Publicly…

Diverse origin and nature of tumor-infiltrating lymphocytes: the infection hypothesis

In the 19th century, Rudolf Virchow observed lymphocyte infiltration in tumors and suggested a potential link between cancer and inflammation. Current explanations for the origin of tumor-infiltrating lymphocytes are based on the interaction between c…

Sleeping Beauty mutagenesis identifies BACH2 and other regulators of CD8+ T-cell exhaustion, persistence in vivo, and CAR-T cell function under tumor-associated chronic antigen stimulation

Background
Genes that enhance T-cell function represent promising targets for improving engineered T-cell therapies for cancer. While extensive CRISPR knockout screens have identified key genes enhancing T-cell persistence, employing Sleeping Beauty (…

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