IL-4-STAT6-induced high Siglec-G/10 expression aggravates the severe immune suppressive tumor microenvironment and impedes the efficacy of immunotherapy in head and neck squamous cell carcinoma

Background
Immune checkpoint blockade therapy has shown limited efficacy in head and neck squamous cell carcinoma (HNSCC). Sialic acid binding immunoglobulin-like lectin (Siglec)-15 has been identified as a novel immune evasion biomarker, while the ro…

Tumor-intrinsic TTLL12 drives resistance to cancer immunotherapy via modulating myeloid-derived suppressor cells

Background
The majority of patients treated with immunotherapy as a standalone therapy experience little to no benefits. Tubulin tyrosine ligase 12 (TTLL12), as a member of the tubulin tyrosine ligase protein family, is associated with the prognosis o…

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…

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