Data from Activation of Tumor-Cell STING Primes NK-Cell Therapy

• DOI: 10.1158/2326-6066.c.6550907.v1
• Publication Date: 2023-04-04T19:34:53Z
• Authors: Erik H. Knelson; Elena V. Ivanova; Mubin Tarannum; Marco Campisi; Patrick H. Lizotte; Matthew A. Booker; Ismail Ozgenc; Moataz Noureddine; Brittany Meisenhe...; Minyue Chen; Brandon Piel; Nathaniel Spicer; Bonje Obua; Cameron M. Messier; Erin Shannon; Navin R. Mahadevan; Tetsuo Tani; Pieter J. Schol; Anna M. Lee-Hassett; Ari Zlota; Ha V. Vo; Minh Ha; Arrien A. Bertram; Saemi Han; Tran C. Thai; Corinne E. Gustafson; Kartika Venugopal; Timothy J. Haggerty; Thomas P. Albertson; Antja-Voy Hartley; Pinar O. Eser; Ze-Hua Li; Israel Cañadas; Marina Vivero; Assunta De Rienzo; William G. Richards; Adnan O. Abu-Yousif; Vicky A. Appleman; Richard C. Gregory; Alexander Parent; Neil Lineberry; Eric L. Smith; Pasi A. Jänne; Juan J. Miret; Michael Y. Tolsto...; Rizwan Romee; Cloud P. Paweletz; Raphael Bueno; David A. Barbie
• Keywords: Sting; CXCR3

<div>Abstract<p>Activation of the stimulator interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding mechanism action in human tumors is key developing therapeutic combinations that activate effective innate immunity. Here, we report malignant pleural mesothelioma cells robustly express and are responsive agonist treatment <i>ex vivo</i>. Using dynamic single-cell RNA sequencing explants treated with a agonist, observed CXCR3 chemokine activation primarily tumor cancer-associated fibroblasts, as well T-cell cytotoxicity. In contrast, primary natural killer (NK) resisted agonist–induced enhanced migration killing NK mesothelin-targeted chimeric antigen receptor (CAR)-NK cells, improving activity patient-derived organotypic spheroids. These studies reveal fundamental importance using samples assess cellular immune therapies. By functionally profiling elevated expression uncovered distinct consequences humans support testing combining CAR-NK cell therapies.</p></div>