Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control

Margaret P Manspeaker; Meghan J O'Melia; Susan N Thomas

doi:10.1136/jitc-2022-005079

Elicitation of stem-like CD8⁺ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control

J Immunother Cancer. 2022 Sep;10(9):e005079. doi: 10.1136/jitc-2022-005079.

Authors

Margaret P Manspeaker^{1

2}, Meghan J O'Melia³, Susan N Thomas^{4

3

5

6}

Affiliations

¹ Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
² School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
³ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
⁴ Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA susan.thomas@gatech.edu.
⁵ George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
⁶ Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.

Abstract

Background: Tumor-draining lymph nodes (TdLNs) are critical in the regulation of local and systemic antitumor T cell immunity and are implicated in coordinating responses to immunomodulatory therapies.

Methods: Biomaterial nanoparticles that deliver chemotherapeutic drug paclitaxel to TdLNs were leveraged to explore its effects in combination and immune checkpoint blockade (ICB) antibody immunotherapy to determine the benefit of TdLN-directed chemoimmunotherapy on tumor control.

Results: Accumulation of immunotherapeutic drugs in combination within TdLNs synergistically enhanced systemic T cell responses that led to improved control of local and disseminated disease and enhanced survival in multiple murine breast tumor models.

Conclusions: These findings suggest a previously underappreciated role of secondary lymphoid tissues in mediating effects of chemoimmunotherapy and demonstrate the potential for nanotechnology to unleashing drug synergies via lymph node targeted delivery to elicit improved response of breast and other cancers.

Keywords: Breast Neoplasms; Drug Therapy, Combination; Immunomodulation; Immunotherapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms* / drug therapy
CD8-Positive T-Lymphocytes
Female
Humans
Immunomodulation
Immunotherapy*
Lymph Nodes
Mice

Abstract

Publication types

MeSH terms

Grants and funding