Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program
Recommended Citation
Weiss J, Gibbons K, Ehyaee V, Perez-Silos V, Zevallos A, Maienschein-Cline M, Brister E, Sverdlov M, Shah E, Balakrishna J, Symes E, Frederiksen JK, Gann PH, Post R, Lopez-Hisijos N, Reneau J, Venkataraman G, Bailey N, Brown NA, Xu ML, Wilcox RA, Inamdar K, and Murga-Zamalloa C. Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program. Am J Pathol 2023.
Document Type
Article
Publication Date
1-1-2024
Publication Title
The American journal of pathology
Abstract
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
PubMed ID
37923249
ePublication
ePub ahead of print
Volume
194
Issue
1
First Page
165
Last Page
178
