Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma
Anusha Kalbasi, Mito Tariveranmoshabad, Kevin Hakimi, Sarah Kremer, Katie M. Campbell, Juan M. Funes, Agustin Vega-Crespo, Giulia Parisi, Ameya Champekar, Christine Nguyen, Davis Y. Torrejon, Daniel Sanghoon Shin, Jesse M. Zaretsky, Robert Damoiseaux, Daniel E. Speiser, Pedro P. López‐Casas, Marisol Quintero, Antoni Ribas
Abstract
tumors. BO-112 activated double-stranded RNA (dsRNA) sensing (via protein kinase R and Toll-like receptor 3) and induced MHC I expression via nuclear factor κB, independent of both IFN signaling and NLRC5. In summary, we demonstrated that in the absence of tumor IFN signaling, MHC I expression is essential and sufficient for the efficacy of ACT. For tumors lacking MHC I expression due to deficient IFN signaling, activation of dsRNA sensors by BO-112 affords an alternative approach to restore the efficacy of ACT.