scholarly journals Comparative analysis of post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation reveals differences in the tumor microenvironment

2020 ◽  
Author(s):  
Mathis Overkamp ◽  
Massimo Granai ◽  
Irina Bonzheim ◽  
Julia Steinhilber ◽  
Jens Schittenhelm ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tumor Microenvironment ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoproliferative Disorders ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Post Transplant

AbstractPost-transplant lymphoproliferative disorders (PTLD) occur after solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HCT) and are frequently associated with Epstein-Barr virus (EBV). Because of the complex immune setup in PTLD patients, the tumor microenvironment (TME) is of particular interest to understand PTLD pathogenesis and elucidate predictive factors and possible treatment options. We present a comparative study of clinicopathological features of 48 PTLD after HCT (n = 26) or SOT (n = 22), including non-destructive (n = 6), polymorphic (n = 23), and monomorphic (n = 18) PTLD and classic Hodgkin lymphoma (n = 1). EBV was positive in 35 cases (73%). A detailed examination of the TME with image analysis-based quantification in 22 cases revealed an inflammatory TME despite underlying immunosuppression and significant differences in its density and composition depending on type of transplant, PTLD subtypes, and EBV status. Tumor-associated macrophages (TAMs) expressing CD163 (p = 0.0022) and Mannose (p = 0.0016) were enriched in PTLD after HCT. Double stains also showed differences in macrophage polarization, with more frequent M1 polarization after HCT (p = 0.0321). Higher counts for TAMs (CD163 (p = 0.0008) and cMaf (p = 0.0035)) as well as in the T cell compartment (Granzyme B (p = 0.0028), CD8 (p = 0.01), and for PD-L1 (p = 0.0305)) were observed depending on EBV status. In conclusion, despite the presence of immunosuppression, PTLD predominantly contains an inflammatory TME characterized by mostly M1-polarized macrophages and cytotoxic T cells. Status post HCT, EBV positivity, and polymorphic subtype are associated with an actively inflamed TME, indicating a specific response of the immune system. Further studies need to elucidate prognostic significance and potential therapeutic implications of the TME in PTLD.

Malignancy Following Solid Organ and Hematopoietic Stem Cell Transplantation

2009 ◽  
Vol 02 ◽  
pp. 49
Author(s):  
Angela Susanne Punnett ◽  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immunosuppressive Agents ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Increased Risk

There is a growing appreciation of the increased risk for malignancy following solid organ and hematopoietic stem cell transplantation as the survival of these patient populations increases overall. The risk for malignancy is related to a complex interaction of type, degree, and duration of immunosuppression, viral status, and recipient age. Most of the malignancies documented are common in the general population but occur with increasing incidence and have significant implications for post-transplant surveillance. Post-transplant lymphoproliferative disorder is specific to the transplant population and remains a treatment challenge. The development of novel immunosuppressive agents, the use of individualized immunosuppressive regimens, and collaborative therapeutic trials are necessary to advance clinical care for these patients. This article will review the current issues around malignancy in the post-transplant patient population.

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