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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1507938

Circulating immune landscape in melanoma patients undergoing anti-PD1 therapy reveals key immune features according to clinical response to treatment

Provisionally accepted
Eleonora Sosa Cuevas Eleonora Sosa Cuevas 1Stéphane Mouret Stéphane Mouret 2Guillaume Vayssière Guillaume Vayssière 1Siham Kerboua Siham Kerboua 1Pauline Girard Pauline Girard 1Jean-Paul Molens Jean-Paul Molens 1Marc Monceau Marc Monceau 2Julie Charles Julie Charles 2Philippe Saas Philippe Saas 1CAROLINE ASPORD CAROLINE ASPORD 1*
  • 1 INSERM U1209 Institut pour l'Avancée des Biosciences (IAB), La Tronche, France
  • 2 Centre Hospitalier Universitaire de Grenoble, La Tronche, Rhône-Alpes, France

The final, formatted version of the article will be published soon.

    Immune checkpoint blockers (ICB) bring unprecedented clinical success, yet many patients endure immune mediated adverse effects and/or fail to respond. Predictive signatures of response to ICB and mechanisms of clinical efficacy or failure remain understudied. DC subsets, in network with conventional αβ T (Tconv), NK, γδ T and iNKT cells, harbor pivotal roles in tumor control, yet their involvement in response to ICB remained underexplored. We performed an extensive longitudinal monitoring of circulating immune cells from melanoma patients treated with first-line anti-PD1, before (T0) and during treatment. We assessed the phenotypic and functional features of DC and effector cells' subsets by multi-parametric flow cytometry and ProcartaPlex® dosages. We revealed differences according to response to treatment and modulations of patterns during treatment, highlighting a strong link between the immune landscape and the outcome of anti-PD1 therapy. Responders exhibited higher frequencies of circulating cDC1s, CD8 + T cells, and γδ2 + T cells in central memory (CM) stage. Notably, we observed a distinct remodeling of ICP expression profile, activation status and natural cytotoxicity receptor patterns of immune subsets during treatment. Anti-PD1 modulated DCs' functionality and triggered deep changes in the functional orientation of Tconv and γδT cells. Overall, our work provides new insights into the immunological landscape sustaining favorable clinical responses or resistance to first-line anti-PD1 therapy in melanoma patients. Such exploration participates in uncovering the mechanism of action of anti-PD1, discovering innovative predictive signatures of response, and paves the way to design pertinent combination strategies to improve patient clinical benefits in the future.

    Keywords: immunomonitoring, Anti-PD1 therapy, Melanoma, clinical response, T cells

    Received: 08 Oct 2024; Accepted: 15 Nov 2024.

    Copyright: © 2024 Sosa Cuevas, Mouret, Vayssière, Kerboua, Girard, Molens, Monceau, Charles, Saas and ASPORD. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: CAROLINE ASPORD, INSERM U1209 Institut pour l'Avancée des Biosciences (IAB), La Tronche, France

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