Programmed death 1 ligand (PD-L1) in solid cancers after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Nagasaki Transplant Group

Abstract

Programmed death 1 ligand (PD-L1) is an immunomodulatory molecule expressed by cancer cells, and it has been widely demonstrated to inhibit host antitumor responses. The aim of the present study was to identify clinicopathological features associated with PD-L1 expression in the secondary solid cancers of patients after allogeneic hematopoietic stem cell transplantation. In this database of 530 patients who received allo-HSCT between 1990 and 2017, 15 developed solid cancers with a median interval of 3487 days after transplantation. Three patients had 2 different solid cancers. Eighteen solid cancer cases were identified. A multivariate analysis showed that chronic graft-versus-host disease (GVHD) was associated with an increased risk of solid cancer. The presence of chronic GVHD was observed in 8 out of 18 cases at the diagnosis of secondary malignancies. PD-L1 expression levels in cancers were significantly higher in patients with active chronic GVHD than in those without chronic GVHD (P = 0.020). Five cases of cancer that developed in the involved organs of chronic GVHD showed 30% or higher PD-L1 positivity. The present results revealed distinct PD-L1 expression in the secondary solid cancers of post-transplant patients with chronic GVHD.

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Acknowledgements

The authors thank the many hematologists at Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, for the diagnosis and treatment of post-transplant patients with solid cancers. This work was partly supported by the grant from Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in Aid for Young Scientists (B) (#17K16189) for H.I..

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SK, HI, and YM conceived and designed the study; SK, HI, TK, DI, MF, TF, SS, YS, J.T., and YM collected samples and clinical data; SK and DN performed pathological assessments; SK and HI performed statistical analyses; SK, HI, HM, KO, and YM interpreted the data; SK, HI, and YM wrote the manuscript and created the figures and tables; and all the authors critically reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to Hidehiro Itonaga.

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This study was approved by the Ethics Committees of Nagasaki University Hospital (approval no. 18052108–4), Sasebo City General Hospital (approval no. 2018-A020), the National Hospital Organization Nagasaki Medical Center (approval no. 30034), and Nagasaki Prefecture Gotochuoh Hospital (approval no. 30–4) at which this study was performed.

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Kasai, S., Itonaga, H., Niino, D. et al. Programmed death 1 ligand (PD-L1) in solid cancers after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Nagasaki Transplant Group. Int J Hematol (2020). https://doi.org/10.1007/s12185-020-02926-6

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Keywords

  • Allogeneic transplantation
  • Graft-versus-host disease
  • Hematopoietic stem cell transplantation
  • PD-L1
  • Second cancer