Expression of activating NK-cell receptors is a hallmark of the innate-like T-cell neoplasm in peripheral T-cell lymphomas

Summary

Peripheral T- or 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 histologic 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 of angioimmunoblastic T-cell lymphoma, 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 LILRB1 was detected in 14 (64%) cases, whereas activating receptors DNAM1, NKp46, and NKG2D were expressed in seven (32%), nine (41%), and five (23%) cases, respectively. Although LILRB1 was detected regardless of the disease entities, the activating NK-cell receptors were expressed predominantly in TIA-1-positive neoplasms (DNAM1, 49%; NKp46, 69%; and NKG2D, 38%, respectively). 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 the different cell of origin from NK and innate-like T cells. Furthermore, NKG2D expression showed a negative impact on survival among the examined 22 cases, which mainly received the standard chemotherapy regimen (log-rank test, P =0.024). We propose that the presence of the activating NK-cell receptors may provide new insights into the understanding of peripheral T-cell lymphomas and characterizes them as the innate-like T-cell neoplasm.

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