Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1.

An AI-Ready Multiplex Staining Dataset for Reproducible and Accurate Characterization of Tumor Immune Microenvironment.

We introduce a new AI-ready computational pathology dataset containing restained and co-registered digitized images from eight head-and-neck squamous cell carcinoma patients. Specifically, the same tumor sections were stained with the expensive multiplex immunofluorescence (mIF) assay first and then restained with cheaper multiplex immunohistochemistry (mIHC). This is a first public dataset that demonstrates the equivalence of these two staining methods which in turn allows several use cases; due to the equivalence, our cheaper mIHC staining protocol can offset the need for expensive mIF staining/scanning which requires highly-skilled lab technicians.

An AI-Ready Multiplex Staining Dataset for Reproducible and Accurate Characterization of Tumor Immune Microenvironment.

We introduce a new AI-ready computational pathology dataset containing restained and co-registered digitized images from eight head-and-neck squamous cell carcinoma patients. Specifically, the same tumor sections were stained with the expensive multiplex immunofluorescence (mIF) assay first and then restained with cheaper multiplex immunohistochemistry (mIHC). This is a first public dataset that demonstrates the equivalence of these two staining methods which in turn allows several use cases; due to the equivalence, our cheaper mIHC staining protocol can offset the need for expensive mIF staining/scanning which requires highly-skilled lab technicians.

γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer.

Immune checkpoint blockade has been largely unsuccessful for the treatment of bone metastatic castrate-resistant prostate cancer (mCRPC). Here, we report a combinatorial strategy to treat mCRPC using γδ-enriched chimeric antigen receptor (CAR) T cells and zoledronate (ZOL). In a preclinical murine model of bone mCRPC, γδ CAR-T cells targeting prostate stem cell antigen (PSCA) induced a rapid and significant regression of established tumors, combined with increased survival and reduced cancer-associated bone disease.