Nanoparticle interactions with immune cells dominate tumor retention and induce T cell–mediated tumor suppression in models of breast cancer
Journal
Science Advances
Journal Volume
6
Journal Issue
13
Date Issued
2020
Author(s)
Korangath P.
Barnett J.D.
Sharma A.
Henderson E.T.
Stewart J.
Kandala S.K.
Yang C.-T.
Caserto J.S.
Hedayati M.
Armstrong T.D.
Jaffee E.
Gruettner C.
Zhou X.C.
Fu W.
Hu C.
Sukumar S.
Simons B.W.
Ivkov R.
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. Copyright ? 2020 The Authors, some rights reserved.
SDGs
Other Subjects
Antibodies; Antigen-antibody reactions; Cytology; Diseases; Mammals; Medical nanotechnology; Nanoparticles; T-cells; Tumors; Antibody-antigen interactions; Cancer immunotherapy; Critical variables; Microenvironments; Nanoparticle interaction; Nanoparticle technologies; Systemic deliveries; Therapeutic activity; Immune system; antibody conjugate; immunological antineoplastic agent; iron; nanoparticle; protein binding; tumor marker; animal; biopsy; breast tumor; CD8+ T lymphocyte; disease model; drug effect; drug screening; female; human; immunology; immunomodulation; metabolism; mouse; pathology; T lymphocyte; tumor associated leukocyte; tumor cell line; tumor microenvironment; tumor volume; Animals; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Biopsy; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Disease Models, Animal; Female; Humans; Immunoconjugates; Immunomodulation; Iron; Lymphocytes, Tumor-Infiltrating; Mice; Nanoparticles; Protein Binding; T-Lymphocytes; Tumor Burden; Tumor Microenvironment; Xenograft Model Antitumor Assays
Publisher
American Association for the Advancement of Science
Type
journal article