Immune checkpoint inhibitors reverse tolerogenic mechanisms induced by melanoma targeted radionuclide therapy.

ABSTRACT: In line with the ongoing phase I trial (NCT03784625) dedicated to melanoma targeted radionuclide therapy (TRT), we explore the interplay between immune system and the melanin ligand [¹³¹I]ICF01012 alone or combined with immunotherapy (immune checkpoint inhibitors, ICI) in preclinical models. Here we demonstrate that [¹³¹I]ICF01012 induces immunogenic cell death, characterized by a significant increase in cell surface-exposed annexin A1 and calreticulin. Additionally, [¹³¹I]ICF01012 increases survival in immunocompetent mice, compared to immunocompromised (29 vs. 24 days, p = 0.0374). Flow cytometry and RT-qPCR analyses highlight that [¹³¹I]ICF01012 induces adaptive and innate immune cell recruitment in the tumor microenvironment. [¹³¹I

SUBMITTER: Rouanet J 

PROVIDER: S-EPMC11027634 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature