Tumor immune microenvironment (TIME) characterization of prostate cancer bone metastasis may guide future immunotherapies

Authors

• B Chatterjee
• S Boudjadi
• PR Pandey
• H Kim
• W Sun
• FG Barr

Abstract

Background:
Prostate cancer (PCa) is the most common malignancy among men in the US.1 PCa is considered a cold tumor because immune cells (IC) are suppressed. PCa can spread to bone (bone metastasis, or “mets”). To design immunotherapies that target PCa bone mets, it is important to characterize their TIME.
Methods:
We procured bone mets tissue samples (n=13) from 9 patients with castration-resistant PCa. EDTA was used to optimally preserve bone tissue. Adjacent FFPE bone mets were stained using 3 validated multiplex immunofluorescence panels and opal technology. We identified the lymphocytes (CD4+ and CD8+ T cells), tumor-associated macrophages (M1 and M2), and myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs) infiltrating the bone mets. Densities of these cells were calculated per mm2 of the analytes.
Results:
In all PCa bone mets samples, suppression of ICs was apparent. On average, M2 macrophages, important pro-metastatic cells, were almost 4-fold and 52-fold greater than CD8+ and CD4+ T cells, respectively. M2:M1 macrophage ratio was 1.44. PMN-MDSC and M-MDSC were 38 and 9, respectively. HLA-DR– expression was 27-fold greater than HLA-DR+. HLA class I will be examined in future endeavors.
Conclusion:
Our data agree with previous studies about the immune-excluded TIME of PCa. HLA-DR–, MDSCs, and M2 macrophage predominance over T lymphocytes promotes IC suppression. Thus, there is agreement that targeting M2 macrophages and promoting M2 to M1 polarization may control PCa bone mets.

1. Siegel, R., Miller, K., Wagle, N., Jemal, A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023; 73: 17–48.

Scientific Focus Area: Clinical Research

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