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Human cancer cells xenografts to assess the efficacy of granulysin-based therapeutics.

Methods Cell Biol

January 2025

Apoptosis, Immunity and Cancer Group, Aragón Health Research Institute (IIS-Aragón), University of Zaragoza, Zaragoza, Spain. Electronic address:

9-kDa Granulysin is a protein present in the granules of human activated cytotoxic T lymphocytes and natural killer cells. It has been shown to exert cytolytic activity against a wide variety of microbes: bacteria, fungi, yeast and protozoa. Recombinant isolated granulysin is also capable of inducing tumor cell death, so it could be used as an anti-tumor therapy.

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Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.

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Background: B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 across various solid tumors and developed novel monoclonal antibodies (mAbs) targeting B7-H3 for CAR T cell therapy.

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Interdisciplinary Oncology, University of British Columbia, Vancouver, BC, Canada; MAPcore, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Assessment of the tumor immune microenvironment can be used as a prognostic tool for improved survival and as a predictive biomarker for treatment benefit, particularly from immune modulating treatments including cytotoxic chemotherapy. Using Digital Spatial Profiling (DSP), we studied the tumor immune microenvironment of 522 breast cancer cases by quantifying 35 immune biomarkers on tissue microarrays from the MA.5 phase III clinical trial.

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Pharmaceutics

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NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.

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