Cancer-associated MSC drive tumor immune exclusion and resistance to immunotherapy, which can be overcome by Hedgehog inhibition
Sandra Cascio, Chelsea Chandler, Linan Zhang, Sarah Sinno, Bingsi Gao, Sayali Onkar, Tullia C. Bruno, Dario A.A. Vignali, Haider Mahdi, Hatice U. Osmanbeyoglu, Anda Vlad, Lan Coffman, Ronald J. Buckanovich
Abstract
phenotype. Both monocytes and macrophages express high levels of transforming growth factor β–induced (Tgfbi) protein, which suppresses NK cell activity. Hedgehog inhibitor (HHi) therapy reversed CA-MSC effects, reducing myeloid cell presence and expression of Tgfbi, increasing intratumoral NK cell numbers, and restoring response to ICI therapy. Thus, CA-MSCs regulate antitumor immunity, and CA-MSC hedgehog signaling is an important target for cancer immunotherapy.
Topics & Concepts
Immune systemImmunotherapyCancerCancer immunotherapyCancer researchHedgehogImmunologyBiologyMedicineCell biologySignal transductionInternal medicineCancer Immunotherapy and BiomarkersPhagocytosis and Immune RegulationImmune cells in cancer