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Stem cell transplantation

Pretransplant nivolumab further enhanced Treg expansion after posttransplant cyclophosphamide; another aspect for immune tolerance by PTCy after nivolumab

Leukemia volume 35, pages 929–931 (2021)Cite this article

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We read the article by Nieto et al. with interest [1]. The authors demonstrated that pretransplant nivolumab resulted in a high frequency of IFN-γ-producing effector T cells that might contribute severe graft-versus-host disease (GVHD) after transplant. They also showed that posttransplant cyclophosphamide (PTCy) abrogated the immune activations and could suppress GVHD to the mild levels. The data were comprehensive and convincing, but the analyses of regulatory T cells (Tregs) were limited to just a one-time point. In general, PTCy can contribute to enhancing Treg recovery as well as suppressing alloreactive effector T cells [2,3,4]. Our previous study suggested that programmed cell death 1 (PD-1) plays an important role in Treg homeostasis [5]. Moreover, by using a murine HSCT model, we recently demonstrated that pretransplant PD-1 blockade critically impaired posttransplant Treg recovery, leading to severe GVHD, and PTCy could restore Treg homeostasis and ameliorate GVHD [6]. Based on these findings, we herein analyzed the chronological recovery of Treg after PTCy in patients with or without pretransplant nivolumab therapy and considered the impact of nivolumab on Treg homeostasis after PTCy-based transplant.

We experienced three cases of chemotherapy-refractory classical Hodgkin lymphoma, those were treated by nivolumab as a salvage therapy and followingly received HLA-haploidentical HSCT. The clinical courses of the three patients are described in Supplementary Fig. 1. We compared the detailed immune reconstitutions of patients receiving pretransplant nivolumab followed by PTCy-based HLA-haploidentical HSCT (“Nivo→PTCy”; Cases 1 and 2) and ATG-based HLA-haploidentical HSCT (“Nivo→ATG”; Case 3) with those of patients who received PTCy-based HLA-haploidentical HSCT without ICI (“control-PTCy”; Cases 4–6) and ATG-based HLA-haploidentical HSCT without ICI (“control-ATG”; Cases 7–9), as respective controls. Clinical data and frozen samples were collected from these nine patients. Detailed patient characteristics and transplant outcomes are summarized in supplementary Table 1. All patients provided written informed consent before sample collection.

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Fig. 1: Comparison of the reconstitution of Treg among Nivo→PTCy, control-PTCy, Nivo→ATG, and control-ATG treatment groups.

References

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Acknowledgements

The authors would like to thank Kyoko Maeda and Hiromi Nakashima for help with obtaining clinical samples. This work was supported by research funding from the Japan Society for the Promotion of Science KAKENHI (Grant No. 20K08753) to KM.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Shuntaro Ikegawa, Yusuke Meguri, Kentaro Mizuhara, Takuya Fukumi, Hiroki Kobayashi, Yuichi Sumii, Takumi Kondo, Yasuhisa Sando, Miki Iwamoto, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda & Ken-ichi Matsuoka

  2. Department of Hematology and Blood Transfusion, Kochi Health Sciences Center, Kochi, Japan

    Yuka Fujisawa & Toshi Imai

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  1. Shuntaro Ikegawa
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Correspondence to Ken-ichi Matsuoka.

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Ikegawa, S., Meguri, Y., Mizuhara, K. et al. Pretransplant nivolumab further enhanced Treg expansion after posttransplant cyclophosphamide; another aspect for immune tolerance by PTCy after nivolumab. Leukemia 35, 929–931 (2021). https://doi.org/10.1038/s41375-021-01167-8

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