Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program

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The American journal of pathology


Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare and relatively indolent B-cell lymphoma. Characteristically, the [lymphocyte-predominant (LP)] tumor cells are embedded in a microenvironment enriched in lymphocytes. More aggressive variants of mature B-cell and peripheral T-cell lymphomas exhibit nuclear expression of the polo-like kinase 1 (PLK1) protein, stabilizing c-MYC and associated with worse clinical outcomes. We demonstrate frequent expression of PLK1 in the LP cells in NLPHL cases (100%; n = 76). In contrast, <5% of classic Hodgkin lymphoma cases (n = 70) show PLK1 expression within the tumor cells. Loss-of-function approaches demonstrated that the expression of PLK1 promotes cell proliferation and increased c-MYC stability in NLPHL cell lines. Correlation with clinical parameters revealed that the increased expression of PLK1 was associated with advanced-stage disease in patients with NLPHL. A multiplex immunofluorescence panel coupled with artificial intelligence algorithms was used to correlate the composition of the tumor microenvironment with the proliferative stage of LP cells. The results showed that LP cells with PLK1 (high) expression were associated with increased numbers of cytotoxic and T-regulatory T cells. Overall, the findings demonstrate that PLK1 signaling increases NLPHL proliferation and constitutes a potential vulnerability that can be targeted with PLK1 inhibitors. In addition, the findings suggest that an active immune surveillance program in NLPHL may be a critical mechanism limiting PLK1-dependent tumor growth.

Medical Subject Headings

Humans; Artificial Intelligence; Hodgkin Disease; Lymphocytes; Lymphoma, B-Cell; Polo-Like Kinase 1; Tumor Microenvironment

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ePub ahead of print





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