Chrystal Paulos, Professor and Co-leader of the Cancer Immunology Program at Winship Cancer Institute of Emory University, shared a post on LinkedIn about a paper she co-authored with colleagues published in Cancer Immunology Research:
“Excited to share new work from our group, recently published in Cancer Immunology Research.
Our study uncovers how neoantigen avidity fundamentally programs CD8+ T cell behavior and dictates the success of adoptive immunotherapy in solid tumors.
Using a controlled melanoma model where just three amino acids distinguish a low-avidity antigen from a high-avidity neoantigen, we found:
- High-avidity neoantigen drives rapid T cell activation, strong effector function, and durable tumor regression
- The lymph node acts as the essential education hub – Potent cell therapy depends on early LN priming to succeed
- Blocking LN egress early collapses therapy, while later blockade has minimal impact
- Naïve and stem-memory T cells outperform effector-expanded cells, which cannot efficiently enter lymph nodes
- Host lymphocytes aren’t required — high-avidity priming enables the transferred CD8 T cell product alone to eliminate tumors
These results point to a clear principle:
Durable adoptive immunotherapy requires the right T cell, the right antigen, and the right timing within the lymph node microenvironment.
When these align, long-term tumor control becomes achievable!
This work was led by first author Megen Wittling, with Hannah Knochelmann, and myself (Chrystal Paulos) as co-corresponding last authors — and strengthened by the creativity, rigor, and teamwork of many colleagues across our collaborating institutions Winship Cancer Institute of Emory University, Medical University of South Carolina, and Stanford University School of Medicine.”
Title: T cell priming by high avidity neoantigens in lymph nodes augments adoptive immunotherapy
Authors: Megen C. Wittling, Amalia M. Rivera Reyes, Megan M. Wyatt, Anna C. Cole, Aubrey S. Smith, Guillermo O. Rangel Rivera, James H. Carmouche, Kailey G. Diatikar, Ayana T. Ruffin, Michael B. Ware, Frances J. Bennett, Connor J. Dwyer, Riley M.F. Pihl, Soundharya Kumaresan, Gregory B. Lesinski, Chrystal M. Paulos, Hannah M. Knochelmann
You can read the full article in Cancer Immunology Research.
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