Tumor-Draining Lymph Nodes Contain Immunodominant Peptide-Specific T Cells which Demonstrate Efficacy in Murine Models of Adoptive Immunotherapy

Kevin Choong, John Ammori, Khaled Hamzeh, Hallie Graor, Julian Kim

University Hospitals Cleveland Medical Center, Division of Surgical Oncology, Cleveland, OH, USA. Maui Medical Group, Department of Surgery, Kahului, HI, USA


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Background:  The purpose of this study was to determine whether tumor draining lymph nodes (TDLNs) contain the necessary components to process and present tumor-rejection antigens. The secondary objective was to determine whether short term ex vivo culture of TDLNs could generate peptide-reactive T cells with specific anti-tumor effector function in vivo.

Methods:  4T1 and RENCA cancer cell lines were transfected with an expression plasmid containing HER2. These cell lines were then inoculated into the mammary fat pads of BALB/c mice to generate TDLNs. The antigen-experienced CD62Llow T cell subpopulation of TDLNs was isolated and activated ex vivo with anti-CD3 and expanded in interleukin (IL)-2 prior to determining in vitro and  in vivo activity.

Results:  Of nine HER2 nonameric peptides synthesized using the SYFPIETHI prediction model, culture activated cells derived from TDLNs from HER2-bearing 4T1 cells (4T1.2) secreted significant levels of interferon-g in response to the highest affinity peptide TYLPTNASL. Furthermore, culture-activated cells derived from 4T1.2 TDLNs secreted significant levels of interferon-g when co-cultured with either 4T1.2 or HER2-transfected RENCA cells, but not RENCA transfected with control plasmid. Additionally, adoptive transfer of culture activated cells derived from 4T1.2 TDLNs cured mice bearing 4T1, 4T1.2 and RENCA-HER2 but not RENCA transfected with control plasmid.

Conclusions:  Short-term culture of TDLNs ex vivo results in generation of peptide-reactive T cells which can be expanded and cure mice bearing HER2 transfected tumors in vivo. These results provide proof-of-concept that TDLNs have the capacity to process and present tumor-rejection antigens, specific to an individual patient’s tumor. Journal of Nature and Science (JNSCI), 3(6):e398, 2017



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