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High numbers of programmed cell death-1-positive tumor infiltrating lymphocytes correlate with early onset of post-transplant lymphoproliferative disorder

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Abstract

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation. In addition to reactivation of Epstein–Barr virus in immunocompromised patients, impaired tumor immunity is suggested to be a risk factor for PTLD. However, it remains unclear whether immune suppressive tumor-infiltrating lymphocytes (TILs) correlate with the occurrence or prognosis of PTLD. We analyzed TILs in 26 patients with PTLD to elucidate the clinicopathological significance of the expression of PD-1 and FoxP3, which are associated with exhausted T-cells and regulatory T-cells (Tregs), respectively. Numbers of PD-1+ TILs in the PTLD specimens were significantly higher in patients who developed PTLD early after transplantation (P = 0.0040), while numbers of FoxP3+ TILs were not (P = 0.184). There was no difference in overall response rate regardless of the expression of PD-1 or FoxP3. FoxP3high patients tended to have a shorter time to progression compared with FoxP3low patients, especially in the case of FoxP3high patients with diffuse large B-cell lymphoma-subtype PTLD (P = 0.011), while PD-1high patients did not. These results suggest that T-cell exhaustion may be mainly associated with PTLD development, while immune suppression by Tregs may be dominant in enhanced progression of PTLD following disease occurrence.

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Acknowledgements

This work was supported by the Japan Society for the Promotion of Science (KAKENHI grant no. 19K07450).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan

    Hideaki Saito, Hirohiko Shibayama, Jun Toda, Shinsuke Kusakabe, Michiko Ichii, Jiro Fujita, Kentaro Fukushima, Tetsuo Maeda, Masao Mizuki, Takafumi Yokota, Yuzuru Kanakura & Naoki Hosen

  2. Department of Pathology, Kurume University School of Medicine, Kurume, Japan

    Hiroaki Miyoshi, Masao Seto & Koichi Ohshima

  3. Department of Hematology, Suita Municipal Hospital, Osaka, Japan

    Tetsuo Maeda

  4. Department of Hematology, Graduate School of Medical Sciences, International University of Health and Welfare, Chiba, Japan

    Kenji Oritani

  5. Department of Hematology, Sumitomo Hospital, Osaka, Japan

    Yuzuru Kanakura

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  1. Hideaki Saito
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  2. Hiroaki Miyoshi
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  3. Hirohiko Shibayama
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Contributions

Contribution: H. Saito, HM, H. Shibayama, MS, and K.Ohshima were responsible for study conception and design; H. Saito, HM, and K. Ohshima performed collection and assembly of data; JT, SK, MI, JF, KF, TM, MM, K. Oritani, and TY performed collection of data; H. Saito, HM, H. Shibayama, MS, TY, YK, NH, and K. Ohshima analyzed and interpreted data, and wrote the manuscript; and all authors approved the final manuscript.

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Correspondence to Hirohiko Shibayama.

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Saito, H., Miyoshi, H., Shibayama, H. et al. High numbers of programmed cell death-1-positive tumor infiltrating lymphocytes correlate with early onset of post-transplant lymphoproliferative disorder. Int J Hematol 114, 53–64 (2021). https://doi.org/10.1007/s12185-021-03129-3

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