Macrophage Infiltration Correlates with Genomic Instability in Classic Hodgkin Lymphoma

Abstract

Hodgkin lymphoma (HL) is a biologically diverse group of lymphoid tumors, which accounts for 1% of all de novo neoplasms in the world’s population. It is divided into two main groups: the more common classic Hodgkin lymphoma (cHL) and the less common nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). cHL is further divided into four subtypes, which differ in morphology and the contents of tumor microenvironment. Macrophages are one of the components of tumor microenvironment known to contribute to creating an immunosuppressive microenvironment, which inhibits the activity of cells expressing granzyme B against tumor cells, even when tumor cells are infected with Epstein–Barr virus (EBV). Our research aimed to explore the association between the specific contents of tumor microenvironment and the genetic anomalies in tumor cells. The presence and the relative percentage of cytotoxic T lymphocytes and macrophages was detected by immunohistochemical staining of the antigens specific for certain cell populations. Fluorescent in situ hybridization was used to detect anomalies in the genome of tumor cells and in situ hybridization was used to detect the presence of EBV. Our results show an association between the number of CD163+ macrophages and the number of TP53 copies or BCL6 gene translocation. Patients who had a higher number of CD163+ macrophages infiltrating tumor tissue and three or higher number of copies of TP53 showed poorer survival. We conclude that the presence of macrophages may contribute to genetic instability in cHL, which drives the progression of cHL and decreases survival of the patients.

Unraveling the Immune Microenvironment in Classic Hodgkin Lymphoma: Prognostic and Therapeutic Implications

“…Another mechanism in which TAMs might promote tumor growth is supposed to be the induction of the genetic instability of HRS cells, probably through the release of free radicals which contribute to a mutagenic microenvironment. This was based on the observation that TP53 amplification in neoplastic cells, linked with poorer patients’ survival, was associated with increased infiltration by M2 macrophages [ 65 ].…”

Tumor microenvironment in Hodgkin lymphoma: novel prognostic factors for assessing disease evolution

“…The literature extensively reports that overexpression of CD68+ cells in the tumor microenvironment is associated with decreased progression-free survival (PFS), overall survival (OS), and increased risk of relapse [19][20][21][22]. Different hypotheses suggest that macrophages promote genetic instability within the tumor microenvironment, thereby impacting patient survival [23][24][25].…”

Macrophage-Based Therapeutic Strategies in Hematologic Malignancies

“…Studies have shown that the presence of CD163 + macrophages in tumor tissue is related to poor survival in patients with classical Hodgkin lymphoma (CHL) [303]. Additionally, a lower number of TAMs in CHL samples was correlated with a higher progressionfree survival rate [304].…”