Bibliographic Details
| Title: |
GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses |
| Authors: |
Abhishek S. Kashyap, Laura Fernandez-Rodriguez, Yun Zhao, Gianni Monaco, Marcel P. Trefny, Naohiro Yoshida, Kea Martin, Ashwani Sharma, Natacha Olieric, Pankaj Shah, Michal Stanczak, Nicole Kirchhammer, Sung-Moo Park, Sebastien Wieckowski, Heinz Laubli, Rachid Zagani, Benjamin Kasenda, Michel O. Steinmetz, Hans-Christian Reinecker, Alfred Zippelius |
| Source: |
Cell Reports, Vol 28, Iss 13, Pp 3367-3380.e8 (2019) |
| Publisher Information: |
Elsevier, 2019. |
| Publication Year: |
2019 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
Biology (General), QH301-705.5 |
| More Details: |
Summary: Dendritic cell (DC) activation is a critical step for anti-tumor T cell responses. Certain chemotherapeutics can influence DC function. Here we demonstrate that chemotherapy capable of microtubule destabilization has direct effects on DC function; namely, it induces potent DC maturation and elicits anti-tumor immunity. Guanine nucleotide exchange factor-H1 (GEF-H1) is specifically released upon microtubule destabilization and is required for DC activation. In response to chemotherapy, GEF-H1 drives a distinct cell signaling program in DCs dominated by the c-Jun N-terminal kinase (JNK) pathway and AP-1/ATF transcriptional response for control of innate and adaptive immune responses. Microtubule destabilization, and subsequent GEF-H1 signaling, enhances cross-presentation of tumor antigens to CD8 T cells. In absence of GEF-H1, anti-tumor immunity is hampered. In cancer patients, high expression of the GEF-H1 immune gene signature is associated with prolonged survival. Our study identifies an alternate intracellular axis in DCs induced upon microtubule destabilization in which GEF-H1 promotes protective anti-tumor immunity. : Certain chemotherapeutics elicit potent anti-tumor immunity. Kashyap et al. demonstrate that microtubule-destabilizing chemotherapeutics induce maturation of dendritic cells through activation of microtubule-associated protein GEF-H1. This leads to effective priming of CD8 T cells against tumor antigens. GEF-H1 is critical for anti-tumor immunity of microtubule-targeting chemotherapy. Keywords: GEF-H1, lfc, dendritic cells, microtubule-targeting agents, cross presentation, JNK pathway, ansamitocin-P3, plinabulin, immunotherapy, chemotherapy |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124719311052; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2019.08.057 |
| Access URL: |
https://doaj.org/article/21a0d97cff3b46a0a90aae9154512253 |
| Accession Number: |
edsdoj.21a0d97cff3b46a0a90aae9154512253 |
| Database: |
Directory of Open Access Journals |
