{Reference Type}: Journal Article
{Title}: CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy.
{Author}: Franken A;Bila M;Mechels A;Kint S;Van Dessel J;Pomella V;Vanuytven S;Philips G;Bricard O;Xiong J;Boeckx B;Hatse S;Van Brussel T;Schepers R;Van Aerde C;Geurs S;Vandecaveye V;Hauben E;Vander Poorten V;Verbandt S;Vandereyken K;Qian J;Tejpar S;Voet T;Clement PM;Lambrechts D;
{Journal}: Immunity
{Volume}: 57
{Issue}: 3
{Year}: 2024 Mar 12
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2024.02.007
{Abstract}: Cancer patients often receive a combination of antibodies targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA4). We conducted a window-of-opportunity study in head and neck squamous cell carcinoma (HNSCC) to examine the contribution of anti-CTLA4 to anti-PD-L1 therapy. Single-cell profiling of on- versus pre-treatment biopsies identified T cell expansion as an early response marker. In tumors, anti-PD-L1 triggered the expansion of mostly CD8+ T cells, whereas combination therapy expanded both CD4+ and CD8+ T cells. Such CD4+ T cells exhibited an activated T helper 1 (Th1) phenotype. CD4+ and CD8+ T cells co-localized with and were surrounded by dendritic cells expressing T cell homing factors or antibody-producing plasma cells. T cell receptor tracing suggests that anti-CTLA4, but not anti-PD-L1, triggers the trafficking of CD4+ naive/central-memory T cells from tumor-draining lymph nodes (tdLNs), via blood, to the tumor wherein T cells acquire a Th1 phenotype. Thus, CD4+ T cell activation and recruitment from tdLNs are hallmarks of early response to anti-PD-L1 plus anti-CTLA4 in HNSCC.