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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Updated: Sep 14, 2025

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
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Tumour progression shows decrease in PD-L1 expression in matched metastases/primary uveal melanomas.

Maria Chiara Gelmi1, Gulçin Gezgin1, Ellen Kapiteijn2

  • 1Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.

Acta Ophthalmologica
|July 24, 2025
PubMed
Summary
This summary is machine-generated.

Metastatic uveal melanoma (UM) shows lower PD-L1 expression and higher T-cell infiltration than primary UM, potentially explaining poor response to immune checkpoint inhibitors (ICI). Primary tumors may benefit more from ICI therapy.

Keywords:
immune checkpointmetastasesmicroenvironmentuveal melanoma

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Area of Science:

  • Oncology
  • Immunology
  • Pathology

Background:

  • Immune checkpoint inhibitors (ICI) have transformed cancer treatment but show limited efficacy in metastatic uveal melanoma (UM).
  • Understanding the tumor microenvironment in UM is crucial for improving ICI therapy outcomes.

Purpose of the Study:

  • To investigate the expression of PD-1, PD-L1, T-cell, and macrophage markers in primary and metastatic UM.
  • To elucidate the reasons behind the unsatisfactory response to ICI in metastatic UM.

Main Methods:

  • Immunohistochemical (IHC) staining of 32 UM samples (13 primary, 19 metastases) for PD-L1, PD1, CD3, CD4, CD8, CD68, CD163, HLA class I, and BAP1.
  • Quantitative and semiquantitative scoring of markers and comparison between primary and metastatic UM, including matched cases.

Main Results:

  • Metastatic UM exhibited significantly lower PD-L1 expression on tumor cells compared to primary UM.
  • UM metastases showed increased T-cell infiltration (including PD1 expression) but no difference in macrophage infiltration.
  • Low HLA Class I expression in metastases correlated with absent PD-L1 and PD1 expression; BAP-1 loss was linked to higher lymphocytic infiltration.

Conclusions:

  • Lower PD-L1 expression in UM metastases, despite increased lymphocytic infiltrate, may explain the limited effectiveness of ICI.
  • Primary UM might be more responsive to ICI therapy than metastases.
  • Targeting primary tumors in a neoadjuvant or adjuvant setting could be beneficial for high-risk patients.