Tumor Microenvironment Determinants of Immunotherapy Response Identified By Integrated Host &amp; Viral Analysis of Post-Transplant Lymphoproliferative Disorders

Schroers‐Martin, Joseph; Garofalo, Andrea; Soo, Joanne; Boegeholz, Jan; Alig, Stefan; Sworder, Brian; Liu, Chih Long; Luikart, Helen; Gamino, Gerardo; Morales, DP; Freystätter, Kathrin; Hamilton, James N.; Kurtz, David M.; Hollander, Seth A.; Rosenthal, David N.; Dhillon, Gundeep; Raikhelkar, J.; Verleden, Stijn E.; Nijland, Marcel; Agbor‐Enoh, Sean; Andreas, Martin; Kfoury, Abdallah G.; Ross, Heather J.; Zaffiri, Lorenzo; Natkunam, Yasodha; Diehn, Maximilian; Khush, Kiran K.; Alizadeh, Ash A.

doi:10.1182/blood-2022-158647

Cited by 2 publications

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“…Recently, a multidimensional characterization of PTLD TME and virome presented distinct immunogenomic features reflecting divergent PTLD biology. 28 Here, we show that the PT-ABCL TME is heterogenous and can be classified as inflamed and non-inflamed according to the proportions of distinct immune cells. Although the PT-ABCL TME is affected by the immunosuppressive therapy, a subset of patients displayed higher expression of cytotoxicity gene signature and an inflamed TME rich in T cells, translating to improved survival.…”

Section: Discussionmentioning

confidence: 76%

Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas

et al. 2023

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Post-transplant lymphoproliferative disorders (PTLDs) are iatrogenic immune deficiencyassociated lymphoid/plasmacytic proliferations developing due to immunosuppression in solid organ or hematopoietic stem cell allograft patients. PTLDs are characterized by abnormal proliferation of lymphoid cells and have a heterogeneous clinical behavior. We profiled expression of >700 tumor microenvironment (TME)-related genes in 75 post-transplant aggressive B-cell lymphomas (PT-ABCLs). EBV-positive PT-ABCLs clustered together and were enriched for type I interferon pathway and antiviral response genes. Additionally, a cytotoxicity gene signature associated with EBV-positivity and favorable overall survival (OS; HR 0.61, P=0.019). In silico immunophenotyping revealed two subgroups with distinct immune cell compositions. The inflamed subgroup with higher proportions of immune cells had better outcome compared to non-inflamed subgroup (median OS >200.0 vs. 15.2 months, P=0.006). In multivariable analysis with EBV status, International Prognostic Index, and rituximab-containing treatment, the inflamed TME remained as an independent predictor for favorable outcome. We also compared the TME between posttransplant and immunocompetent host diffuse large B-cell lymphomas (DLBCLs) (n=75) and discovered that the proportions of T cells were lower in PT-DLBCL. In conclusion, we provide a comprehensive phenotypic characterization of PT-ABCLs, highlighting the importance of immune cell composition of TME in determining the clinical behavior and prognosis of PT-ABCL.

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Section: Discussionmentioning

confidence: 76%

Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas

et al. 2023

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How I treat posttransplant lymphoproliferative disorder

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2023

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Post-transplant lymphoproliferative disorder (PTLD) is an important and potentially life-threatening complication of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT). Given the heterogeneity of PTLD and the risk of infectious complications in immunosuppressed patients, treatment of this disease remains challenging. Monomorphic PTLD and lymphoma of B-cell origin account for the majority of cases. Treatment strategies for PTLD consist of response-adapted risk-stratified methods using immunosuppression reduction, immunotherapy, and/or chemotherapy. With this approach, approximately 25% of patients do not need chemotherapy. Outcomes for patients considered high-risk or who do not respond to frontline therapies remain dismal, and novel treatments are needed in this setting. PTLD is associated with Epstein-Barr virus infection in 60-80% of cases making EBV-directed therapy an attractive treatment modality. Recently, the introduction of adoptive immunotherapies represents a promising option for refractory cases; hopefully these treatment strategies can be used in earlier lines of therapy in the future.

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Tumor Microenvironment Determinants of Immunotherapy Response Identified By Integrated Host & Viral Analysis of Post-Transplant Lymphoproliferative Disorders

Cited by 2 publications

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Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas

Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas

How I treat posttransplant lymphoproliferative disorder

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