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

• Authors: Margaret P Manspeaker, Georgia Institute of Technology, Atlanta; Meghan J O'Melia, Emory University; Susan N Thomas, Emory University
• Journal Title: Journal for ImmunoTherapy of Cancer
• Volume: Volume 10, Number 9
• Publisher: BioMed Central | 2022-09-13
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1136/jitc-2022-005079
• Subjects: Engineering, Biomedical
• Keywords: Drug Therapy; Combination; Immunotherapy; Immunomodulation; Breast Neoplasms

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.