2. Academic Validation
  3. Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer

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

  • EMBO Rep. 2023 Jun 27;e55884. doi: 10.15252/embr.202255884.
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
Affiliations

Affiliations

  • 1 Oncoimmunology Group, Navarrabiomed, Hospital Universitario de Navarra, Universidad Publica de Navarra (UPNA), IdISNA, Pamplona, Spain.
  • 2 Medical Oncology Department, Clinica Universidad de Navarra, Madrid, Spain.
  • 3 Program in Solid Tumors, CIMA-University of Navarre-IdISNA, Pamplona, Spain.
  • 4 CIBERONC, Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
  • 5 Department of Biochemistry and Genetics, School of Sciences, University of Navarra-IdISNA, Pamplona, Spain.
  • 6 Program in Gene Therapy and Regulation of Gene Expression, CIMA-University of Navarra-IdISNA, Pamplona, Spain.
  • 7 Lung Cancer and Respiratory Diseases Unit, Center for Biomedical Research of La Rioja (CIBIR), Fundación Rioja Salud, Logroño, Spain.
  • 8 Department of Oncology, Hospital Universitario de Navarra-IdISNA, Pamplona, Spain.
  • 9 Cancer Center University of Navarra (CCUN), Pamplona, Spain.
  • 10 Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra-IdISNA, Pamplona, Spain.
  • 11 Pathological Anatomy Service, Hospital Universitario San Pedro, Rioja Salud, Logroño, Spain.
  • 12 Pneumology Service, Rioja Salud, Logroño, Spain.
  • 13 Fundación Jiménez Díaz, Madrid, Spain.
  • 14 Centro de Salud Salazar-Ezcároz, Navarra, Spain.
  • 15 Spanish Biomedical Research Networking Centre, CIBERES, Madrid, Spain.
  • 16 Program in Immunology and Immunotherapy, CIMA-University of Navarra-IdISNA, Pamplona, Spain.
  • # Contributed equally.
PMID: 37366231 DOI: 10.15252/embr.202255884
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.

Keywords

NK cells; adenocarcinoma; biomarker; monocytes; neutrophils.

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