Tumor-draining lymph nodes are survival niches that support T cell priming against lymphatic transported tumor antigen and effects of immune checkpoint blockade in TNBC

• Authors: Meghan J O'Melia, Emory University; Margaret Manspeaker, Georgia Institute of Technology; Susan N Thomas, Emory University
• Journal Title: CANCER IMMUNOLOGY IMMUNOTHERAPY
• Volume: Volume 70, Number 8
• Publisher: Springer (part of Springer Nature) | 2021-08-01, Pages 2179-2195
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s00262-020-02792-5
• Subjects: Engineering, Biomedical; Engineering, Mechanical
• Keywords: triple-negative breast cancer; lymph nodes; tumor dissemination; immune checkpoint blockade; T cell priming; drug delivery

Abstract

Triple negative breast cancer (TNBC) is a significant clinical problem to which immunotherapeutic strategies have been applied with limited success. Using the syngeneic E0771 TNBC mouse model, this work explores the potential for anti-tumor CD8+ T cell immunity to be primed extratumorally in lymphoid tissues and therapeutically leveraged. CD8+ T cell viability and responses within the tumor microenvironment (TME) were found to be severely impaired, effects coincident with local immunosuppression that is recapitulated in lymphoid tissues in late stage disease. Prior to onset of a locally suppressed immune microenvironment, however, CD8+ T cell priming within lymph nodes (LN) that depended on tumor lymphatic drainage remained intact. These results demonstrate tumor-draining LNs (TdLN) to be lymphoid tissue niches that support the survival and antigenic priming of CD8+ T lymphocytes against lymph-draining antigen. The therapeutic effects of and CD8+ T cells response to immune checkpoint blockade were furthermore improved when directed to LNs within the tumor-draining lymphatic basin. TdLNs therefore represent a unique potential tumor immunity reservoir in TNBC for which strategies may be developed to improve the effects of ICB immunotherapy. Precís Here, we show that tumor-draining lymph nodes are niches that support the survival and antigenic priming of CD8+ T cells and show an easily implementable method of leveraging lymph nodes within the tumor basin to improve breast cancer immunotherapy outcomes.