12 research outputs found
Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors
<div><p>Introduction</p><p>The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs.</p><p>Methods</p><p>Tumor tissues from 23 patients with WHO Type B2/B3 thymoma (n = 12) and thymic carcinoma (n = 11) were identified and clinical outcomes were annotated. The expression of membranous PD-L1 on tumor cells, CD3+ and CD8+ tumor infiltrating lymphocytes (TILs), co-stimulatory (CD137, GITR, ICOS), and co-inhibitory immune checkpoint molecules (PD-1, CTLA-4, TIM-3) were assessed semi-quantitatively using immunohistochemistry.</p><p>Results</p><p>PD-L1 positivity (≥ 25% of tumor membrane expression) was frequent in TETs (15/23, 65%), more common in thymomas compared to thymic carcinomas (p<0.01), and was associated with longer overall survival (p = 0.02). TIM-3 and GITR were expressed in all TETs, including 18/23 and 12/23 with at least moderate/high expression, respectively. Moderate/high CD137 expression correlated with CD8+ (p = 0.01) and moderate/high GITR expression co-associated with PD-1 (p = 0.043).</p><p>Conclusions</p><p>TETs are characterized by frequent PD-L1 expression and PD-L1 is associated with improved survival, suggesting PD-L1 signaling may be biologically important in TETs. Robust expression of markers of immune activation and immunotherapeutic target molecules in TETs emphasizes the potential for development of anti-PD-1/PD-L1 therapies.</p></div
Histologic subtype and correlation with PD-L1 expression, CD8+ T-cells and CD3+ T-cells.
<p>Histologic subtype and correlation with PD-L1 expression, CD8+ T-cells and CD3+ T-cells.</p
Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors - Fig 3
<p>Associations of immune marker expression and TILs with overall survival from time of initial diagnosis <b><i>A</i></b>, PD-L1 expression, where <25 deemed negative, ≥25 deemed positive. <b><i>B</i></b>, CD3+ T-cells where 0/1 staining by IHC deemed low, 2/3 deemed high. <b><i>C</i></b>, CD3+ T-cells where 0/1 staining by IHC deemed low, 2/3 deemed high.</p
CD8 semiquantitative scoring scheme: Scoring for each specimen took into account the heterogeneity of TIL densities throughout the entire section of each tumor, here showing representative images of 1+ (A), 2+ (B) and 3+ (C) scores for CD8 representing numbers of immuno-labeled TILs per 40X microscopic field in the range of 1–30, 31–100, and >100, respectively.
<p>CD8 semiquantitative scoring scheme: Scoring for each specimen took into account the heterogeneity of TIL densities throughout the entire section of each tumor, here showing representative images of 1+ (A), 2+ (B) and 3+ (C) scores for CD8 representing numbers of immuno-labeled TILs per 40X microscopic field in the range of 1–30, 31–100, and >100, respectively.</p
Heatmap of p-values of pairwise association analysis of co-stimulatory and co-inhibitory immune checkpoint molecules and TILs.
<p>Markers were compared as binary values, M-score: defined as ≥25 of 100 cells with positive membranous staining of PD-L1, all other markers evaluated by immunohistochemistry, where 0/1 = low positive T cell staining, 2/ 3+ = moderate-high positive T cell staining.</p
Association of clinical factors with cumulative incidence of subsequent brain metastasis in patients who did not experience brain metastasis at baseline.
<p>Association of clinical factors with cumulative incidence of subsequent brain metastasis in patients who did not experience brain metastasis at baseline.</p
Association of serum biomarkers with cumulative incidence of subsequent brain metastasis in patients who did not experience brain metastasis at baseline.
<p>Association of serum biomarkers with cumulative incidence of subsequent brain metastasis in patients who did not experience brain metastasis at baseline.</p
Distribution of serum biomarkers and other factors by presence of brain metastases at baseline or development of subsequent brain metastases after baseline.
<p>Distribution of serum biomarkers and other factors by presence of brain metastases at baseline or development of subsequent brain metastases after baseline.</p
Univariate logistic regression analysis for association of biomarkers with presence of brain metastasis at baseline.
<p>Univariate logistic regression analysis for association of biomarkers with presence of brain metastasis at baseline.</p