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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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STAT3, tumor microenvironment, and microvessel density in diffuse large B cell lymphomas.

Roberto Tamma1, Giuseppe Ingravallo2, Francesco Gaudio3

  • 1Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, Bari, Italy.

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|October 19, 2019
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Summary

Activated STAT3 in diffuse large B-cell lymphoma (DLBCL) correlates with poor survival. In activated B-cell (ABC) DLBCL, higher STAT3 expression is linked to increased inflammatory cells, angiogenesis, and tumor cell proliferation.

Keywords:
DLBCL lymphomasRNAscopeSTAT3lymphocytestumor-associated macrophages

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Area of Science:

  • Oncology
  • Immunology
  • Pathology

Background:

  • Constitutively activated STAT3 is linked to advanced clinical stage and poor survival in diffuse large B-cell lymphoma (DLBCL).
  • Understanding the tumor microenvironment in different DLBCL subtypes is crucial for therapeutic strategies.

Purpose of the Study:

  • To evaluate STAT3 and Ki67 expression, inflammatory cell infiltration, and microvascular density in DLBCL bioptic specimens.
  • To compare these markers between activated B-cell (ABC) and germinal center B (GCB) DLBCL subtypes.

Main Methods:

  • RNA-scope was used to quantify STAT3+ cells.
  • Immunohistochemistry was employed to assess CD3, CD8, CD68, CD163, CD34, and Ki67 positive cells.
  • Correlations between markers were analyzed in ABC and GCB groups.

Main Results:

  • ABC-DLBCL samples showed significantly higher STAT3+ cell counts compared to GCB-DLBCL.
  • Increased infiltration of CD3, CD8, CD68, CD163, CD34, and Ki67 positive cells was observed in ABC patients.
  • Positive correlations were found between STAT3 and inflammatory markers (CD3, CD8, CD68, CD163) in ABC-DLBCL.
  • STAT3 expression correlated with tumor cell proliferation (Ki67) and angiogenesis (CD34) in ABC-DLBCL.

Conclusions:

  • Higher STAT3 expression in ABC-DLBCL is associated with increased infiltration of tumor-associated macrophages (TAMs) and cytotoxic T cells.
  • These findings suggest a role for STAT3 in promoting an inflammatory and angiogenic tumor microenvironment in ABC-DLBCL.
  • STAT3 may represent a therapeutic target in DLBCL, particularly in the ABC subtype.