SITC 2021 | Dysfunction of Tregs and cDC1s in driving resistance to checkpoint blockade immunotherapy in NSCLC

Maria Zagorulya, BS, Koch Institute for Integrative Cancer Research, Cambridge, MA, talks on building on the follow-up study by Dr. Brendan Horton which discovered that a lack of CD8+ T-cell differentiation during priming drives resistance to checkpoint blockade immunotherapy in non-small cell lung cancer (NSCLC). Dr. Zagorulya aims establish how this dysfunction T-cell state is generated. Through investigating this phenomena, regulatory T-cells (Tregs) have been found to play a role in suppressing priming, specifically by suppressing dendritic cells (DCs), conventional type 1 dendritic cells (cDC1s) in particular. As a result, signals 2 and 3 are downregulated and the cytotoxic T-cells remain inactive, preventing the upregulation of effector cells. Thus, the suppression of cDC1s prime a dysfunctional state that which ultimately prevents production of effector molecules. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.