The immune microenvironment of uterine adenosarcomas

Abstract

Background: Uterine adenosarcoma (UA) is an extremely rare sarcoma subtype. There has been limited evaluation of the immune microenvironment in these tumors. The objective of this study is to examine and describe the immune infiltrate and PD-1/PD-L1 expression in UA and to correlate these changes in the tumor micro-environment with the overall survival status or the disease-free survival status (DFSS), respectively.Methods: Patients (pts) treated at our center from 1982 to 2014 with UA were identified. Fifteen cases had tumor paraffin-embedded blocks available. Immunohistochemistry studies for CD3, CD8, FOXP3, CD163, PD-1 and PD-L1 (clone 22C3) were performed. Image analysis was used to assess the density (cells/mm 2 ), except in PD-L1, where the percentage of membranous staining on tumor cells was noted.Results: Immune infiltrate analysis median (range) density in cells/mm 2 varied broadly: CD3 178 (15-802); CD8 117 (11-661); FoxP3 4.8 (0.2-82); CD163 791 (264-1861); and PD1 5 (1-65). 3 cases had rare (1%) PD-L1 tumor membranous labeling. The reports yielded that ten pts were alive, and 5 were dead. Pts who were alive had significant higher CD3 and CD8 median densities in tumors than those who were dead (p = 0.040). There was no correlation between DFSS and CD3 or CD8 median densities. Patients who had no local recurrence had significantly higher CD3 and CD8 median densities in tumors than those who had local recurrence (p = 0.040). Conclusions:In conclusion, this is the first report characterizing the presence of immune infiltrate and PD-1/PD-L1 expression in UA. CD3+ CD8+ T-cells density may be prognostic. The immune-responsiveness of UA needs to be further investigated in a larger study.

The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology, Mutant Type TP53 Expression and Clinical Outcomes

“…26,32,33 An association between high numbers of CD8 + T-lymphocytes, better overall survival, and prolonged recurrence-free survival was indicated in a study conducted by de Jong et al 33 Furthermore, Ali et al showed no correlation between tumor-associated macrophage density and overall survival status in uterine adenosarcoma cases. 20 In contrast, we found the infiltration of higher tumorassociated macrophage counts to be correlated with an unfavorable overall survival and disease-free survival rate. Additionally, Ali et al found that higher CD8 + T-cell density was associated with a better overall survival rate.…”

“…[12][13][14][15][16] A meta-analysis reported by Lu et al showed that elevated PD-L1 expression was correlated with poor differentiation and advanced stages in endometrial cancer, whereas the prognostic effect of PD-L1 on survival was not significant. 15 The expression of PD-L1, along with immune cell infiltration in adenosarcomas, was first reported by Ali et al 20 The authors demonstrated rare (1%) PD-L1 staining in 3 of 15 cases, and found that PD-L1 expression did not affect disease-free survival or overall survival rates. 20 In our series, three of 20 tumors had TPS PD-L1 positivity with a 1% cut-off value and all were high-grade in nature.…”

“…The total number of tumor-associated macrophages and tumor-infiltrating lymphocytes in a tumor area of 1 mm 2 for each patient was used for statistical analysis. 20 Based on the median count of tumor-associated macrophage and tumor-infiltrating lymphocyte as a cut-off, high and low infiltration groups also were defined and used for statistical analysis.…”

Clinical Benefit from Lenvatinib and Pembrolizumab Observed in Mullerian Adenosarcoma: A Case Report

“…Its activity in our patient suggests that it would be worthy of a prospective investigation in mullerian adenosarcoma. In fact, PD-L1 expression, a predictive factor of response to immune checkpoint inhibition, although absent in our case, has been reported in a subset of uterine adenosarcomas [ 10 ].…”

Role of reactive oxygen species in tumors based on the ‘seed and soil’ theory: A complex interaction (Review)

“…Previous studies have found that limited T lymphocyte infiltration or low immunogenicity of the TME is the main reason for the failure of treatment ( 98 , 99 ). The interaction between tumor cells and immune cells is a core feature of the TME ( 100 , 101 ). Owing to the high plasticity of immune cells, tumor cells promote the maturation, differentiation and recruitment of immunosuppressive cells by secreting IL-10, TGF-β, and VEGF to construct an immunosuppressive TME ( 102 , 103 ).…”