Ventura, A. (Alfonso)

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    Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer
    (2023) Tavira, B. (Beatriz); Fernández, L. (Leticia); Kochan, G. (Grazyna); Pio, R. (Rubén); Chocarro, L. (Luisa); Ventura, A. (Alfonso); Alfaro-Arnedo, E. (Elvira); Remirez, A. (Ana); Gotera-Rivera, C. (Carolina); Bocanegra, A. (Ana); Ajona-Martínez-Polo, D. (Daniel); Recalde, N. (Nerea); Piñeiro-Hermida, S. (Sergio); Pichel, J.G. (José G.); Zuazo, M. (Miren); Morilla, I. (Idoia); Fernández-Hinojal, G. (Gonzalo); Blanco, E. (Ester); Echaide, M. (Miriam); Montuenga-Badia, L.M. (Luis M.); Morente, P. (Pilar); Escors, D. (David); Garnica, M. (Maider); Martinez-Aguillo, M. (M.); Roncero, A. (Alejandra); Vera, R. (Ruth); Lasarte, J.J. (Juan José)
    Recent studies highlight the importance of baseline functional immunity for immune checkpoint blockade therapies. High-dimensional systemic immune profiling is performed in a cohort of non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders show high baseline myeloid phenotypic diversity in peripheral blood. To quantify it, we define a diversity index as a potential biomarker of response. This parameter correlates with elevated activated monocytic cells and decreased granulocytic phenotypes. High-throughput profiling of soluble factors in plasma identifies fractalkine (FKN), a chemokine involved in immune chemotaxis and adhesion, as a biomarker of response to immunotherapy that also correlates with myeloid cell diversity in human patients and murine models. Secreted FKN inhibits lung adenocarcinoma growth in vivo through a prominent contribution of systemic effector NK cells and increased tumor immune infiltration. FKN sensitizes murine lung cancer models refractory to anti-PD-1 treatment to immune checkpoint blockade immunotherapy. Importantly, recombinant FKN and tumor-expressed FKN are efficacious in delaying tumor growth in vivo locally and systemically, indicating a potential therapeutic use of FKN in combination with immunotherapy.