#Brafi tcel license
2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.C International License (), which permits unrestricted use, distribution, anc reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. In a large (n = 155) CTCL/PTCL series, PD-L1 was expressed by lymphoma cells in 27% of CTCL and
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Novel therapeutic strategies are urgently needed and clinical trial participation is encouraged for patients afflicted with these T-cell derived NHL. The long-term outlook for patients with advanced-stage cutaneous T-cell lymphomas (CTCL) is similarly discouraging, as durable remissions are rare with existing therapies, and median overall survival for those with nodal and/or visceral organ involvement is 1-2 years. Among peripheral T-cell lymphoma (PTCL) patients ineligible for high-dose therapy and autologous stem-cell transplantation at the time of relapse or progression, median overall survival is less than 6 months. In contrast to these more common B-cell NHL which are curable or controllable with the existing smorgasbord of therapeutic options, including immunochemotherapy and targeted or immunomodulatory agents, T-cell derived NHL, which account for « 10% of NHL in North America, remain an unmet need, as most patients afflicted with these aggressive mature (peripheral) T-cell lymphomas will succumb to their disease within 2 years of diagnosis. While many studies are ongoing, response rates exceeding « 33% have been observed in both diffuse large B-cell and follicular lymphomas. * Correspondence: of InternalMedicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USAĢUniversity of Michigan Comprehensive Cancer Center, 4310 Cancer Center, 1500 East MedicalCenter Drive, Ann Arbor, MI48109, USA Evidence implicating PD-L1 in immune evasion among common B-cell NHL, in conjunction with the high response rates, as high as 87%, observed in relapsed or refractory Hodgkin's lymphoma with PD-1 CPB, provides a strong rationale for this approach in B-cell Genomic alterations involving the PD-L1 (B7-H1, CD274) locus, particularly gene amplification, lead to significant PD-L1 expression in subsets of aggressive B-cell NHL, while lymphoma-associated macrophages within the tumor microenvironment are an abundant source of PD-L1 in others. Like many solid tumors, most non-Hodgkin's lymphomas (NHL) are, to varying degrees, infiltrated by lymphoid-and myeloid-derived cell subsets that contribute to either immune evasion or immunosurveillance. The resurgent interest in the tumor microenvironment, particularly its role in immunosurveillance, and cancer immunotherapy in the past several years may be largely attributed to the successes achieved with immune-checkpoint blockade (CPB) in multiple solid tumors.
Keywords: Checkpoint blockade, Peripheral T-cell lymphoma, Cutaneous T-cell lymphoma, PD-L1 Herein, we review the unique challenges posed by the T-cell lymphoproliferative disorders and discuss potential strategies to optimize checkpoint blockade in these T-cell derived malignancies. While further studies are needed, the available data suggests that responses with PD-1 checkpoint blockade alone will unlikely approach those achieved in other lymphoproliferative disorders.
Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274) expression by malignant T cells and within the tumor microenvironment, provides a strong rationale for therapeutic targeting this immune checkpoint. The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin's lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Tycel Phillips1, Sumana Devata1 and Ryan A. Journal for ImmunoTherapy of Cancer (2016) 4:95 DOI 10.1186/s4042-6Ĭhallenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders