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

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.

• Authors: Hideaki Saito, Hiroaki Miyoshi, Hirohiko Shibayama, Jun Toda, Shinsuke Kusakabe, Michiko Ichii, Jiro Fujita, Kentaro Fukushima, Tetsuo Maeda, Masao Mizuki, Kenji Oritani, Masao Seto, Takafumi Yokota, Yuzuru Kanakura, Naoki Hosen, Koichi Ohshima
• Journal: International journal of hematology (Int J Hematol) Vol. 114 Issue 1 Pg. 53-64 (Jul 2021) ISSN: 1865-3774 [Electronic] Japan
• PMID: 33765256 (Publication Type: Journal Article)

Chemical References

• FOXP3 protein, human
• Forkhead Transcription Factors
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Adult
• Aged
• Female
• Forkhead Transcription Factors (analysis)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Lymphocytes, Tumor-Infiltrating (pathology)
• Lymphoma, Large B-Cell, Diffuse (pathology, therapy)
• Lymphoproliferative Disorders (etiology, pathology)
• Male
• Middle Aged
• Organ Transplantation (adverse effects)
• Programmed Cell Death 1 Receptor (analysis)
• Retrospective Studies
• Young Adult