Development and validation of the Immune Profile Score (IPS), a novel multiomic algorithmic assay for stratifying outcomes in a real-world cohort of patients with advanced solid cancer treated with immune checkpoint inhibitors

Background
Immune checkpoint inhibitors (ICIs) have transformed the oncology treatment landscape. Despite substantial improvements for some patients, the majority do not benefit from ICIs, indicating a need for predictive biomarkers to better inform t…

Super-high tumor mutational burden predicts complete remission following immunotherapy: from Petos paradox to druggable cancer hallmark

Background
The somatic mutation theory predicts that cancer risk should scale proportionally with lifetime cell divisions; yet large-bodied and long-lived species exhibit lower-than-expected cancer incidence—a long-standing contradiction termed …

Single-cell RNA sequencing of baseline PBMCs predicts ICI efficacy and irAE severity in patients with NSCLC

Background
Immune checkpoint inhibitors (ICIs) have transformed treatment and have provided significant clinical benefits and durable responses for patients with advanced non-small cell lung cancer (NSCLC). However, only a small percentage of patients…

Decoding resistance to immune checkpoint inhibitors in non-small cell lung cancer: a comprehensive analysis of plasma proteomics and therapeutic implications

Background
Immune checkpoint inhibitors (ICIs) have shown substantial benefit for patients with advanced non-small cell lung cancer (NSCLC). However, resistance to ICIs remains a major clinical challenge. Here, we perform a comprehensive bioinformatic…

Rationale and feasibility of a rapid integral biomarker program that informs immune-oncology clinical trials: the ADVISE trial

Background
ADVISE (ADaptiVe biomarker trial that InformS Evolution of therapy) (NCT03335540) was a biomarker-adapted feasibility clinical trial of immunohistochemistry (IHC) to inform combination immuno-oncology (I-O) treatment.

Methods
To inform I-O…

Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies

Understanding regional distribution of HLA frequencies is crucial for optimizing enrollment in HLA-restricted clinical trials and to promote trial diversity per the Food and Drug Administration’s 2020 mandate. Using US HLA frequency data and cen…

FMO2+ cancer-associated fibroblasts sensitize anti-PD-1 therapy in patients with hepatocellular carcinoma

Background
The efficacy of immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) is limited by heterogeneity in individual responses to therapy. The heterogeneous phenotypes and crucial roles of cancer-associated fibroblasts (CAFs) in…

B4GALT5 inhibits CD8+ T-cell response by downregulating MHC-I level through ERAD pathway in PDAC

Background
Immune evasion is a crucial event in the progression of pancreatic ductal adenocarcinoma (PDAC). The identification of new immunotherapeutic targets may provide a promising platform for advancing PDAC treatment. This study aims to investiga…

Serum analytes as predictors of disease recurrence and the duration of invasive disease-free survival in patients with triple negative breast cancer enrolled in the OXEL trial treated with immunotherapy, chemotherapy, or chemoimmunotherapy

Background
The OXEL study (NCT03487666) was a phase II trial of patients with triple negative breast cancer (TNBC) with residual disease following neoadjuvant chemotherapy, randomized to receive immunotherapy (anti-programmed cell death protein 1, niv…

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