Publicaciones científicas

Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer

03-ago-2023 | Revista: EMBO Reports

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.

CITA DEL ARTÍCULO  EMBO Rep. 2023 Aug 3;24(8):e55884.  doi: 10.15252/embr.202255884