Bibliographic Details
| Title: |
CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy. |
| Authors: |
Franken, Amelie1,2 (AUTHOR), Bila, Michel1,3,4,5 (AUTHOR), Mechels, Aurelie1,2 (AUTHOR), Kint, Sam1,6,7 (AUTHOR), Van Dessel, Jeroen5 (AUTHOR), Pomella, Valentina8 (AUTHOR), Vanuytven, Sebastiaan6,7 (AUTHOR), Philips, Gino1,2 (AUTHOR), Bricard, Orian1,2 (AUTHOR), Xiong, Jieyi1,2 (AUTHOR), Boeckx, Bram1,2 (AUTHOR), Hatse, Sigrid3,4 (AUTHOR), Van Brussel, Thomas1,2 (AUTHOR), Schepers, Rogier1,2 (AUTHOR), Van Aerde, Cedric9 (AUTHOR), Geurs, Sarah6,7,10 (AUTHOR), Vandecaveye, Vincent11 (AUTHOR), Hauben, Esther11 (AUTHOR), Vander Poorten, Vincent11,12 (AUTHOR), Verbandt, Sara8 (AUTHOR) |
| Source: |
Immunity (10747613). Mar2024, Vol. 57 Issue 3, p541-541. 1p. |
| Subject Terms: |
*T cells, *CYTOTOXIC T lymphocyte-associated molecule-4, *IMMUNOGLOBULIN producing cells, *T cell receptors, *MONONUCLEAR leukocytes |
| 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. [Display omitted] • Addition of anti-CTLA4 to anti-PD-L1 promotes CD4+ T cell expansion in HNSCC • Pre-existing T1 immunity predicts expansion upon anti-PD-L1+anti-CTLA4 treatment • Expanding populations of CD4+ and CD8+ T cells co-localize with DCs and plasma cells • Anti-PD-L1+anti-CTLA4 activates CD4+ T cells in tdLNs, which traffic to the tumor Franken et al. examine the mechanisms that differentiate combined therapy with anti-CTLA4 and anti-PD-L1 from anti-PD-L1 monotherapy in head and neck squamous cell carcinoma (HNSCC). Single-cell analyses of the tumor microenvironment, tumor-draining lymph nodes, and PBMCs of HNSCC patients treated with anti-PD-L1 or anti-PD-L1+anti-CTLA4 reveal CD4+ T cell activation as a hallmark for response to anti-PD-L1+anti-CTLA4 combination therapy. [ABSTRACT FROM AUTHOR] |
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