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Lenalidomide-mediated erythroid improvement in non-del(5q) myelodysplastic syndromes is associated with bone marrow immuno-remodeling

Leukemia volume 32, pages 558–562 (2018)Cite this article

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The impact of lenalidomide on immune regulation of the BM has been documented in MDS.11 Here, responding patients exhibited an upregulation of T cell or B progenitor markers and an increase of T cells and cytotoxic lymphocytes, demonstrating that an adaptive immune response was initiated under therapy. At baseline, MDS patients had a lower abundance of B cells compared with age-matched controls. Very low abundance of B cells is a hallmark of aging related to the decline of lymphoid-biased HSPC.13 This unfitness of B progenitors may be more marked in MDS owing to the accumulation of mutations driving a myeloid bias of hematopoietic hierarchy at the expense of B lymphopoiesis.14 Increased proportions of cytotoxic CD8+ T cells, NK and macrophages have been reported in early MDS by using flow cytometry that measured intra-sample proportions of immune cells within a gated hematopoietic population.15 However, their quantification in the context of BM microenvironment has never been investigated so far. Here, abundance of T CD8+ and cytotoxic lymphocytes was decreased at baseline. This may result from a reduction of naive T-lymphocyte expansion to the benefit of memory T cells related to aging, a specific alteration of T-cell repertoire related to MDS, and an unfitness of mutated T cells.13, 16 Other innate immune cell populations supporting a cytotoxic activity like NK cells, which are thought to accumulate with functional defects in the elderly and in MDS17 were also significantly decreased and did not augment with treatment. To complete the investigation of MDS immunosuppression by using MCP-counter, the validation of specific gene panels for Treg and myeloid-derived suppressive cells is required. In conclusion, the modulation of immune microenvironment by lenalidomide is associated with HI-E. Future investigations will help understanding the architecture of immune cells in the BM microenvironment in these diseases.

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Acknowledgements

We thank A Renneville, C Preudhomme (Lille), O Wagner-Ballon (Créteil) and E Solary (Villejuif) for helpful discussion, S Baulande from ICGex NGS platform of the Institut Curie and investigators of the Groupe Francophone des Myélodysplasies. This study received a research grant from Celgene and was conducted by two teams labeled by the SIRIC Cancer Research for PErsonalized Medicine CARPEM. OK received a CARPEM fellowship grant.

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Author notes

  1. G Kerdivel, V Chesnais and E Becht: These authors contributed equally to this work.

Authors and Affiliations

  1. Department Development, Institut Cochin, Reproduction, Cancer, Paris, France

    G Kerdivel, V Chesnais, F Dumont, N Chapuis, V Boeva, M Fontenay & O Kosmider

  2. Institut National de la Santé et de la recherche médicale INSERM U1016, Paris, France

    G Kerdivel, V Chesnais, F Dumont, N Chapuis, V Boeva, M Fontenay & O Kosmider

  3. Centre National de la recherche scientifique CNRS UMR8104, Paris, France

    G Kerdivel, V Chesnais, F Dumont, N Chapuis, V Boeva, M Fontenay & O Kosmider

  4. Université Paris Descartes, Paris, France

    G Kerdivel, V Chesnais, E Becht, F Dumont, N Chapuis, V Boeva, W H Fridman, M Fontenay & O Kosmider

  5. Team Computational (Epi-)Genetics of Cancer, Paris, France,

    G Kerdivel & V Boeva

  6. Team Normal and pathological hematopoiesis labeled Ligue nationale contre le cancer, Paris, France,

    V Chesnais, N Chapuis, M Fontenay & O Kosmider

  7. INSERM UMR_S1138, Cancer, Immune controls and Escape, Cordeliers Research Center, Paris, France

    E Becht & W H Fridman

  8. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    E Becht

  9. Assistance Publique-Hôpitaux de Paris, Service d’hématologie clinique et Thérapie Cellulaire, Hôpital Henri-Mondor, Créteil, France

    A Toma

  10. Plateforme Paris Descartes de Bioinformatique, Université Paris Descartes, Paris, France

    N Cagnard

  11. Plateforme de Génomique, Institut Cochin, Paris, France

    F Dumont

  12. Assistance Publique-Hôpitaux de Paris, Service d’hématologie biologique, Hôpital Cochin, Paris, France

    A Rousseau, N Chapuis, M Fontenay & O Kosmider

  13. Assistance Publique-Hôpitaux de Paris, Service d’hématologie senior, Hôpital Saint-Louis, Paris, France

    P Fenaux

  14. Assistance Publique-Hôpitaux de Paris, Laboratoire de Biostatistiques et Epidémiologie clinique INSERM UMR-S 717, Hôpital Saint-Louis, Paris, France

    S Chevret

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  1. G Kerdivel
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on behalf of the Groupe Francophone des Myélodysplasies

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Correspondence to M Fontenay.

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Kerdivel, G., Chesnais, V., Becht, E. et al. Lenalidomide-mediated erythroid improvement in non-del(5q) myelodysplastic syndromes is associated with bone marrow immuno-remodeling. Leukemia 32, 558–562 (2018). https://doi.org/10.1038/leu.2017.305

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