Expression of activating natural killer-cell receptors is a hallmark of the innate-like T-cell neoplasm in peripheral T-cell lymphomas.
Cancer Sci, 2018/4;109(4):1254-1262.
Uemura Y[1], Isobe Y[1], Uchida A[1], Asano J[1], Nishio Y[1], Sakai H[1], Hoshikawa M[2], Takagi M[2], Nakamura N[3], Miura I[1]
Affiliations
PMID: 29363227DOI: 10.1111/cas.13512
Impact factor: 6.518
Abstract
Peripheral T- or natural killer (NK)-cell lymphomas are rare and difficult-to-recognize diseases. It remains arduous to distinguish between NK cell- and cytotoxic T-lymphocyte-derived lymphomas through routine histological evaluation. To clarify the cells of origin, we focused on NK-cell receptors and examined the expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms comprising angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive and -negative anaplastic large-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma, aggressive NK-cell leukemia, and other peripheral T-cell lymphomas. Inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) was detected in 14 (64%) cases, whereas activating receptors DNAM1, NKp46, and NKG2D were expressed in 7 (32%), 9 (41%), and 5 (23%) cases, respectively. Although LILRB1 was detected regardless of the disease entity, the activating NK-cell receptors were expressed predominantly in TIA-1-positive neoplasms (DNAM1, 49%; NKp46, 69%; and NKG2D, 38%). In addition, NKp46 and NKG2D were detected only in NK-cell neoplasms and cytotoxic T-lymphocyte-derived lymphomas including monomorphic epitheliotropic intestinal T-cell lymphoma. One Epstein-Barr virus-harboring cytotoxic T-lymphocyte-derived lymphoma mimicking extranodal NK/T-cell lymphoma, nasal type lacked these NK-cell receptors, indicating different cell origin from NK and innate-like T cells. Furthermore, NKG2D expression showed a negative impact on survival among the 22 examined cases, which mainly received the standard chemotherapy regimen (log-rank test, P = .024). We propose that the presence of activating NK-cell receptors may provide new insights into understanding peripheral T-cell lymphomas and characterizing them as innate-like T-cell neoplasm.
Keywords: NK-cell receptor; NKG2D; T/NK-cell lymphoma; cytotoxic molecule; innate-like T cell
MeSH terms
Adult; Aged; Anaplastic Lymphoma Kinase; Antigens, Differentiation, T-Lymphocyte; Female; Humans; Killer Cells, Natural; Leukocyte Immunoglobulin-like Receptor B1; Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; NK Cell Lectin-Like Receptor Subfamily K; Natural Cytotoxicity Triggering Receptor 1; Receptor Protein-Tyrosine Kinases; T-Lymphocytes, Cytotoxic; Young Adult
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