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Ferrata Storti Foundation
Haematologica 2019 Volume 104(8):1626-1632
Non-Hodgkin Lymphoma
Human leukocyte antigen class II expression is a good prognostic factor in adult T-cell leukemia/lymphoma
Mai Takeuchi,1 Hiroaki Miyoshi,1 Naoko Asano,2 Noriaki Yoshida,1,3 Kyohei Yamada,1 Eriko Yanagida,1 Mayuko Moritsubo,1 Michiko Nakata,1 Takeshi Umeno,1 Takaharu Suzuki,1 Satoru Komaki,1 Hiroko Muta,1 Takuya Furuta,1 Masao Seto1 and Koichi Ohshima1
1Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka; 2Department of Molecular Diagnostics, Nagano Prefectural Shinshu Medical Center, Suzaka, Nagano and 3Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan
ABSTRACT
Attenuated human leukocyte antigen (HLA) class I expression is impli- cated as a major immune escape mechanism in several types of tumor. We previously reported that HLA class I/β2 microglobulin and programmed death ligand-1 expression are prognostic factors in adult T-cell leukemia/lymphoma. A recent report suggested that HLA class II expression is also an important prognostic factor for the clinical outcome of programmed death-1 blockade therapy in recurrent/refractory Hodgkin lymphoma. This prompted us to evaluate HLA class II expression in adult T-cell leukemia/lymphoma and to compare the findings with the patients’ clinicopathological features. Of the 132 biopsy specimens examined from newly diagnosed patients, lymphoma cells were positive for HLA class II expression in 44 patients (33.3%), whereas programmed death ligand-1 expression was observed on neoplastic cells from nine patients (6.9%) and on stromal cells in the tumor microenvironment in 83 cases (62.9%). HLA class II-positive cases showed a significantly better overall survival com- pared to the HLA class II-negative cases (P<0.0001). Patients positive for HLA class II and programmed death ligand-1 microenvironmental expres- sion had significantly better prognosis than the other groups (P<0.0001). HLA class II-positive and HLA class II-negative groups also showed a sig- nificant difference in complete remission rate (P=0.0421), HLA class I/β2 microglobulin expression (P=0.0165), and the number of programmed death-1-positive tumor infiltrating cells (P=0.0020). HLA class II expression was a prognostic factor for overall survival both in univariate and multivari- ate analyses (P<0.0001 and P=0.0007, respectively). Our study reveals that HLA class II is a novel prognostic factor in adult T-cell leukemia/lymphoma.
Correspondence:
KOICHI OHSHIMA
ohshima_kouichi@med.kurume-u.ac.jp
Received: August 28, 2018. Accepted: January 9, 2019. Pre-published: January 10, 2019.
doi:10.3324/haematol.2018.205567
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/8/1626
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ARTICLE
Introduction
Adult T-cell leukemia/lymphoma (ATLL), caused by human T-cell lymphotropic virus type 1 (HTLV-1), is an aggressive hematopoietic malignancy with a poor prognosis. HTLV-1 carriers are common in coastal areas of south-western Japan, and approximately 2-5% of carriers develop ATLL in their lifetime.1,2 According to the Shimoyama classification, there are four clinical subtypes of ATLL, namely acute, lymphoma, chronic, and smoldering.3 The acute and lymphoma types are typically associated with a poor prognosis.3 The chronic and smoldering types show better prognosis than the acute and lymphoma types.3 However, half of the cases of chronic ATLL have been reported to transform into leukemia.4
Programmed cell death ligand-1 (PD-L1) is expressed on various tumors and is considered to contribute to tumor immune escape.5-9 We previously reported that PD-L1 expression in tumor cells and stromal cells of the tumor microenvironment are prognostic factors in ATLL.10
Presentation of neoantigens by human leukocyte antigen (HLA) class Ι is required for CD8+ cytotoxic T cells to attack tumor cells. However, the expression of HLA class I and/or its component β2 microglobulin (β2M) is frequently reduced or lost