@article{a27bd89d9a6d4d3dbdc7b9859eb6f93c,
title = "Schweinfurthin induces ICD without ER stress and caspase activation",
abstract = "Our previous study showed that one of the schweinfurthin compounds, 5{\textquoteright}-methoxyschweinfurthin G (MeSG), not only enhances the anti-tumor effect of anti-PD1 antibody in the B16F10 murine melanoma model, but also provokes durable, protective anti-tumor immunity. Here we further investigated the mechanisms by which MeSG treatment induces immunogenic cell death (ICD). MeSG induced significant cell surface calreticulin (CRT) exposure in a time and concentration dependent manner as well as increased phagocytosis of tumor cells by dendritic cells in vitro. Interestingly, this CRT exposure differs from the canonical pathway in several aspects. MeSG does not cause ER stress and does not require PERK to induce CRT exposure. Caspase inhibitors partially rescue cells from MeSG-induced apoptosis, but fail to reduce CRT exposure. MeSG does not cause ERp57 exposure and the absence of ERp57 expression does not reduce CRT exposure. Finally, an intact ER to Golgi transport system is required for this phenomenon. These results lend support to the development of the schweinfurthin family as drugs to enhance clinical response to immunotherapy and highlight the need for additional research on the mechanisms of ICD induction.",
author = "Ruoheng Zhang and Neighbors, {J. D.} and Schell, {T. D.} and Hohl, {R. J.}",
note = "Funding Information: This work was funded by a Penn State University Professorship in Medical Oncology, the Miriam Beckner Cancer Research Endowment and a gift from Highmark to the Penn State Cancer Institute. We thank Jianhong Zhang from Penn State College of Medicine{\textquoteright}s Flow Cytometry Core (RRID:SCR_021134) for assistance with flow cytometry and ImageStream analysis. Amnis ImageStream X Mk II Imaging Cytometer (Luminex, Seattle, Wash) was funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. The compound TTI-3114 (MeSG) was supplied by IOThera Inc. (formerly Terpenoid Therapeutics Inc by Material Transfer Agreement with Penn State College of Medicine). Funding Information: This work was funded by a Penn State University Professorship in Medical Oncology, the Miriam Beckner Cancer Research Endowment and a gift from Highmark to the Penn State Cancer Institute. This work was funded by a Penn State University Professorship in Medical Oncology, the Miriam Beckner Cancer Research Endowment and a gift from Highmark to the Penn State Cancer Institute. We thank Jianhong Zhang from Penn State College of Medicine{\textquoteright}s Flow Cytometry Core (RRID:SCR_021134) for assistance with flow cytometry and ImageStream analysis. Amnis ImageStream X Mk II Imaging Cytometer (Luminex, Seattle, Wash) was funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. The compound TTI-3114 (MeSG) was supplied by IOThera Inc. (formerly Terpenoid Therapeutics Inc by Material Transfer Agreement with Penn State College of Medicine). Publisher Copyright: {\textcopyright} 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2022",
doi = "10.1080/2162402X.2022.2104551",
language = "English (US)",
volume = "11",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "1",
}