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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
microfluidic culture
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.
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
ISSN: 1664-3224
DOI: 10.3389/fimmu.2020.02090
Rights: Attribution 4.0 International
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