%0 Journal Article
%T CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy.
%A Franken A
%A Bila M
%A Mechels A
%A Kint S
%A Van Dessel J
%A Pomella V
%A Vanuytven S
%A Philips G
%A Bricard O
%A Xiong J
%A Boeckx B
%A Hatse S
%A Van Brussel T
%A Schepers R
%A Van Aerde C
%A Geurs S
%A Vandecaveye V
%A Hauben E
%A Vander Poorten V
%A Verbandt S
%A Vandereyken K
%A Qian J
%A Tejpar S
%A Voet T
%A Clement PM
%A Lambrechts D
%J Immunity
%V 57
%N 3
%D 2024 Mar 12
%M 38442708
%F 43.474
%R 10.1016/j.immuni.2024.02.007
%X 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.