Identification of highly immunosupresive treg population in tumor microenvironments

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has abundant immunosuppressive regulatory T cells (Tregs) which contribute to a tumor microenvironment that is resistant to immunotherapy. Tregs in the PDAC tissue, but not those in the spleen, express the αvβ5 integrin in addition to neuropilin-1 (NRP-1), which makes them susceptible to the iRGD tumor-penetrating peptide that targets αv integrin- and NRP1-positive cells. As a result, long-term treatment of PDAC mice with iRGD leads to a tumor-specific decrease of Tregs and improved efficacy of an immune checkpoint blockade. αvβ5 integrin+ Tregs are induced from both naïve CD4+ T cells and natural Tregs upon T cell receptor stimulation, and represent a highly immunosuppressive subpopulation of CCR8+ Tregs. This study identifies αvβ5 integrin as a marker for activated tumor-resident Tregs that can be expanded to achieve tumor-specific Treg depletion to improve anti-tumor immunity for PDAC management.

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