{
  "abstract": "Background Anti-PD-1 monoclonal antibody (mAb) therapy promotes the emergence of new T cell clonotypes within tumors, suggesting de novo priming in the periphery. Yet, the mechanisms that mobilize these additional T cells remain poorly defined.Methods We investigated the impact of anti-PD-1 mAbs on circulating T cell dynamics and their recruitment into tumor-draining lymph nodes (TDLNs) using multiple transgenic mouse models, including FcγR-deficient and type I interferon receptor-deficient mice. To dissect the role of FcγR engagement, we compared an Fc-silent anti-PD-1 LALAPG variant alongside conventional anti-PD-1 antibodies, and further extended our study to an additional immune checkpoint inhibitor for comparison. These approaches were complemented by experiments in FcγR-humanized mice using a human IgG4 anti-PD-1 mAb. In parallel, the effects of the therapeutic IgG4 antibody nivolumab were evaluated in human cell-based assays using dynamic imaging.Results Here, we demonstrate that anti-PD-1 mAbs promote the recruitment of circulating T cells into TDLNs, resulting in an expanded anti-tumor T cell response. This influx was part of a general reactive lymphadenopathy that required FcγR engagement and type I IFN production, leading to a burst of chemokine release. These results were extended to FcgR-humanized mice treated with a human IgG4 variant of the anti-PD-1 mAb and were similarly observed with another immune checkpoint inhibitor, anti-TIM-3, broadening this mechanism as a major one during checkpoint blockade in the LN.Conclusions Our results reveal a previously unrecognized role for low to moderate FcγR engagement in TDLNs, which amplifies the anti-tumor T-cell response elicited during anti-PD-1 therapy.",
  "authors": [
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Marion V Guérin"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Mathilde Ruggiu"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Lea C Feldmann"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Béatrice Corre"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Pauline Ombredanne"
    },
    {
      "affiliations": [
        "INSERM UMR1222, Université Paris Cité, Immunology, Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France"
      ],
      "name": "Bruno Iannascoli"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Zacarias Garcia"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Fabrice Lemaître"
    },
    {
      "affiliations": [
        "Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA"
      ],
      "name": "Lynn Macdonald"
    },
    {
      "affiliations": [
        "Immunology, Institut Pasteur, Paris, France"
      ],
      "name": "Pierre Guermonprez"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Capucine L Grandjean"
    },
    {
      "affiliations": [
        "INSERM UMR1222, Université Paris Cité, Immunology, Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France"
      ],
      "name": "Pierre Bruhns"
    },
    {
      "affiliations": [
        "INSERM U1223, Université Paris Cité, Immunology, Dynamics of Immune Responses, Institut Pasteur, Paris, France"
      ],
      "name": "Philippe Bousso"
    }
  ],
  "title": "Lymph node fine-tuning FcγR signaling boosts anti-PD-1 therapy",
  "uid": "401e5095-5088-58d3-b15a-6f01780842f2"
}