Faculty, Staff and Student Publications

Publication Date

5-1-2024

Journal

Cancer Medicine

DOI

10.1002/cam4.7212

PMID

38686626

PMCID

PMC11058674

PubMedCentral® Posted Date

April 2024

PubMedCentral® Full Text Version

Post-print

Abstract

BACKGROUND: A phase I clinical study for patients with locally advanced H&N cancer with a new class of botanical drug APG-157 provided hints of potential synergy with immunotherapy. We sought to evaluate the efficacy of the combination of APG-157 and immune checkpoint inhibitors.

METHODS: CCL23, UM-SCC1 (human), and SCCVII (HPV-), MEER (HPV+) (murine) H&N cancer cell lines were utilized for in vitro and in vivo studies. We measured tumor growth by treating the mice with APG-157, anti-PD-1, and anti-CTLA-4 antibody combinations (8 groups). The tumor microenvironments were assessed by multi-color flow cytometry, immunohistochemistry, and RNA-seq analysis. Fecal microbiome was analyzed by 16S rRNA sequence.

RESULTS: Among the eight treatment groups, APG-157 + anti-CTLA-4 demonstrated the best tumor growth suppression (p = 0.0065 compared to the control), followed by anti-PD-1 + anti-CTLA-4 treatment group (p = 0.48 compared to the control). Immunophenotype showed over 30% of CD8+ T cells in APG-157 + anti-CTLA-4 group compared to 4%-5% of CD8+ T cells for the control group. Differential gene expression analysis revealed that APG-157 + anti-CTLA-4 group showed an enriched set of genes for inflammatory response and apoptotic signaling pathways. The fecal microbiome analysis showed a substantial difference of lactobacillus genus among groups, highest for APG-157 + anti-CTLA-4 treatment group. We were unable to perform correlative studies for MEER model as there was tumor growth suppression with all treatment conditions, except for the untreated control group.

CONCLUSIONS: The results indicate that APG-157 and immune checkpoint inhibitor combination treatment could potentially lead to improved tumor control.

Keywords

Animals, Mice, CTLA-4 Antigen, Immune Checkpoint Inhibitors, Cell Line, Tumor, Tumor Microenvironment, Head and Neck Neoplasms, Humans, Female, Antineoplastic Combined Chemotherapy Protocols, Programmed Cell Death 1 Receptor, Disease Models, Animal

Published Open-Access

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