Scientific publications
Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer. Scientific Publication
Ana Bocanegra # 1 , Gonzalo Fernández-Hinojal 2 , Daniel Ajona 3 4 5 , Ester Blanco 1 6 , Miren Zuazo 1 , Maider Garnica 1 , Luisa Chocarro 1 , Elvira Alfaro-Arnedo 7 , Sergio Piñeiro-Hermida 1 , Pilar Morente 1 , Leticia Fernández 1 , Ana Remirez 3 , Miriam Echaide 1 , Maite Martinez-Aguillo 8 , Idoia Morilla 8 , Beatriz Tavira 3 9 10 , Alejandra Roncero 11 12 , Carolina Gotera 13 , Alfonso Ventura 14 , Nerea Recalde 14 , José G Pichel 7 15 , Juan José Lasarte 9 16 , Luis Montuenga 3 4 10 , Ruth Vera 8 , Ruben Pio 3 4 5 , David Escors # 1 , Grazyna Kochan # 1
Abstract
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.
CITATION EMBO Rep. 2023 Aug 3;24(8):e55884. doi: 10.15252/embr.202255884
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