Imperial College London
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ProfessorIainMcNeish

Faculty of Medicine, Department of Surgery & Cancer

Chair in Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2185i.mcneish Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

G036Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lau:2020:10.1158/2326-6066.CIR-19-0616,
author = {Lau, TS and Chan, LK-Y and Man, GC-W and Wong, C-H and Lee, JH-S and Yim, S-F and Cheung, T-H and McNeish, I and Kwong, J},
doi = {10.1158/2326-6066.CIR-19-0616},
journal = {Cancer Immunology Research},
pages = {1099--1111},
title = {Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis},
url = {http://dx.doi.org/10.1158/2326-6066.CIR-19-0616},
volume = {8},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Emerging evidence shows that the efficacy of chemotherapeutic drugs are reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated DAMPs (i.e. damage-associated molecular patterns, such as CALR exposure, ATP secretion and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which lead to the activation of NF-κB-mediated CCL2 transcription and IKK2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced ER stress, which triggered PERK activation and eIF2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer.
AU  - Lau,TS
AU  - Chan,LK-Y
AU  - Man,GC-W
AU  - Wong,C-H
AU  - Lee,JH-S
AU  - Yim,S-F
AU  - Cheung,T-H
AU  - McNeish,I
AU  - Kwong,J
DO  - 10.1158/2326-6066.CIR-19-0616
EP  - 1111
PY  - 2020///
SN  - 2326-6066
SP  - 1099
TI  - Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis
T2  - Cancer Immunology Research
UR  - http://dx.doi.org/10.1158/2326-6066.CIR-19-0616
UR  - https://cancerimmunolres.aacrjournals.org/content/8/8/1099
UR  - http://hdl.handle.net/10044/1/79048
VL  - 8
ER  -
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