Nanoparticle interactions with immune cells dominate tumor retention and induce T cell–mediated tumor suppression in models of breast cancer

Preethi Korangath, James D. Barnett, Anirudh Sharma, Elizabeth T. Henderson, Jacqueline Stewart, Shu Han Yu, Sri Kamal Kandala, Chun Ting Yang, Julia S. Caserto, Mohammad Hedayati, Todd D. Armstrong, Elizabeth Jaffee, Cordula Gruettner, Xian C. Zhou, Wei Fu, Chen Hu, Saraswati Sukumar, Brian W. Simons, Robert Ivkov

Research output: Contribution to journalArticlepeer-review

Abstract

The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand (“active targeting”) is superior to its unlabeled counterpart (“passive targeting”). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, and macrophages and not by antibody-antigen interactions. Systemic exposure to either nanoparticle type induced an immune response leading to CD8+ T cell infiltration and tumor growth delay that was independent of antibody therapeutic activity. These results suggest that antitumor immune responses can be induced by systemic exposure to nanoparticles without requiring a therapeutic payload. We conclude that immune status of the host and microenvironment of solid tumors are critical variables for studies in cancer nanomedicine and that nanoparticle technology may harbor potential for cancer immunotherapy.

Original languageEnglish (US)
Article numbereaay1601
JournalScience Advances
Volume6
Issue number13
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • General

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