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https://doi.org/10.3389/fimmu.2020.02090
Title: | Tumor-Derived cGAMP Regulates Activation of the Vasculature | Authors: | Campisi, M. Sundararaman, S.K. Shelton, S.E. Knelson, E.H. Mahadevan, N.R. Yoshida, R. Tani, T. Ivanova, E. Cañadas, I. Osaki, T. Lee, S.W.L. Thai, T. Han, S. Piel, B.P. Gilhooley, S. Paweletz, C.P. Chiono, V. Kamm, R.D. Kitajima, S. Barbie, D.A. |
Keywords: | 2?3?-cGAMP endothelial cells KRAS LKB1 microfluidic culture STING T cell |
Issue Date: | 2020 | Publisher: | Frontiers Media S.A. | Citation: | Campisi, M., Sundararaman, S.K., Shelton, S.E., Knelson, E.H., Mahadevan, N.R., Yoshida, R., Tani, T., Ivanova, E., Cañadas, I., Osaki, T., Lee, S.W.L., Thai, T., Han, S., Piel, B.P., Gilhooley, S., Paweletz, C.P., Chiono, V., Kamm, R.D., Kitajima, S., Barbie, D.A. (2020). Tumor-Derived cGAMP Regulates Activation of the Vasculature. Frontiers in Immunology 11 : 2090. ScholarBank@NUS Repository. https://doi.org/10.3389/fimmu.2020.02090 | Rights: | Attribution 4.0 International | Abstract: | Intratumoral recruitment of immune cells following innate immune activation is critical for anti-tumor immunity and involves cytosolic dsDNA sensing by the cGAS/STING pathway. We have previously shown that KRAS-LKB1 (KL) mutant lung cancer, which is resistant to PD-1 blockade, exhibits silencing of STING, impaired tumor cell production of immune chemoattractants, and T cell exclusion. Since the vasculature is also a critical gatekeeper of immune cell infiltration into tumors, we developed a novel microfluidic model to study KL tumor-vascular interactions. Notably, dsDNA priming of LKB1-reconstituted tumor cells activates the microvasculature, even when tumor cell STING is deleted. cGAS-driven extracellular export of 2?3? cGAMP by cancer cells activates STING signaling in endothelial cells and cooperates with type 1 interferon to increase vascular permeability and expression of E selectin, VCAM-1, and ICAM-1 and T cell adhesion to the endothelium. Thus, tumor cell cGAS-STING signaling not only produces T cell chemoattractants, but also primes tumor vasculature for immune cell escape. © Copyright © 2020 Campisi, Sundararaman, Shelton, Knelson, Mahadevan, Yoshida, Tani, Ivanova, Cañadas, Osaki, Lee, Thai, Han, Piel, Gilhooley, Paweletz, Chiono, Kamm, Kitajima and Barbie. | Source Title: | Frontiers in Immunology | URI: | https://scholarbank.nus.edu.sg/handle/10635/199710 | ISSN: | 1664-3224 | DOI: | 10.3389/fimmu.2020.02090 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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