CancerPathology

Upregulation of TIM3 and reduced expression of PD-1 on immune cell subsets in advanced prostate cancers

Presented in Emirates Pathology, Digital Pathology & Cancer Conference Holiday Inn Dubai, UAE & Virtual
Poster Presenter Name: Dr. Natalia Gorbokon (Germany)

Global Journal of Pathology & Laboratory Medicine
Unified Citation Journals, Pathology 2024, ISSN 2754-0952
Biography: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Niclas C. Blessin, Zhihao Huang, Nicolaus F. Debatin, Elena Bady, Jan H. Müller, Tim Mandelkow, Ronald Simon, Maximillian Lennartz, Christian Bernreuther, Guido Sauter, Till S. Clauditz, Sarah Minner, Eike Burandt, Markus Graefen, Natalia Gorbokon

Abstract:
Although most prostate cancers behave in an indolent manner, a small proportion is highly aggressive. Both primary and advanced prostate cancer is widely known as a non-inflamed cancer that is characterized by a paucity of immune infiltration.
To assess the spatial interplay of TIM3, CTLA-4, and PD-1/-L1 expressing leukocyte subpopulations in 453 prostate cancers, tissue microarrays were stained with 21 antibodies using our BLEACH&STAIN multiplex fluorescence immunohistochemistry approach and analyzed using a deep learning-based image analysis framework.
The immune cell density of CD8+ cytotoxic T-cells, CD4+ T-helper cells, FOXP3+ regulatory T-cells, M1/ M2 macrophages, as well as CD11c+ dendritic cells increased consistently along with the Gleason grade in primary prostate cancer (p≤ 0.034 each).
In recurrent prostate cancers under therapy, the density of FOXP3+ regulatory T-cells and M1 macrophages further increased, while the density of CD8+ cytotoxic T-cells, CD4+ T-helper cells, as well as CD11c+ dendritic cells decreased (p≤0.017 each). Although expression of TIM3 on T-cell subsets, macrophages and dendritic cells was upregulated in advanced/ recurrent tumors, the expression level of PD-1 was downregulated in all analyzed T-cell subsets.
Although prostate cancer is generally considered a low inflamed tumor, the degree of tumor infiltration by various immune cell subtypes increases markedly along with tumor progression and in recurrent tumors under therapy. Taken together, these data suggest that the evaluation of the spatial distribution of immune cell types along with their immune checkpoint protein expression can provide relevant clinical information in prostate cancer.

Keywords: TIM3, prostate cancer, tissue microarray, multiplex fluorescence immunohistochemistry, immune checkpoint

Tags:
Cancer, Immunodeficiency States, Immunophenotyping, Molecular Diagnostics & Proteomics, Evolutionary Medicine, Functional Identification & Biomarkers, Hematopoietic & other Malignancies, Anatomical Pathology, Clinical Pathology, Dermato Pathology, Forensic Pathology, Hemato Pathology, Histopathology, Molecular Pathology, Surgical Pathology, Histopathology, Chemical Pathology, Hematopathology, Histopathology, Cytopathology, Forensic Pathology, Dermatopathology, Clinical Biochemistry, Infection Control, Cytokines, Enzymology, Endocrinology, Cellular Lineage, Virology, Rheology, Toxicology, Neuropathology, Diagnostic Pathology, Mesothelial Proliferations, Transfusion medicine, Clinical microbiology, Cytogenetics, Molecular Genetics Pathology, Immunopathology, Veterinary Pathology, Anatomical Pathology, General Pathology

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