Event Series

IIG Seminar Series

Event Description

Immune checkpoints blockade established the proof of principle that activation of T effector immune function can significantly improve cancer outcome. However, current the majority of patients fail to respond to checkpoint blockade therapy, likely because many immunosuppressive mechanisms cannot be overcome with checkpoint blockade alone. T cells effector programs are instructed and modulated by professional antigen presenting cells (APC) that populate tumor lesions. Yet very little is known about the molecular wiring of APC in the tumor microenvironment. Here we used CITE-Seq to profile 600,000 immune cells in tumor and adjacent tumor-free tissues from 35 patients with lung cancer lesions. We also used CITE-Seq to profile APC that reside in experimental lung cancer lesions. We identified the molecular profile of APC that accumulate in tumors compared to the adjacent tissues and explored the functional relevance of these programs in experimental lung cancers. We show that most APC co-express both immunogenic and suppressive pathways that reduce their functionality in tissues. Specifically, we found that Th2 cytokines produced by tumor cells significantly contribute to limiting APC immunogenicity and to promoting APC -driven immunoregulation of T cell and NK cell effector function in the tumor microenvironment. These data emphasize the benefit of blocking Th2 response in epithelial tumors to enhance APC functionality and promote antitumor immunity.

Hosted By

Gregoire Altan-Bonnet