[557] B7-H1 Expression in Merkel Cell Carcinoma and Co-Localization with Immune Infiltrates

Jeremy G Vincent, Evan J Lipson, Haiying Xu, Janis M Taube. Johns Hopkins Hospital, Baltimore, MD

Background: B7-H1 expression by antigen presenting cells is a normal mechanism for inducing immune tolerance. Many tumor types have been shown to co-opt this mechanism, facilitating escape from immunosurveillance and therapeutic regimens. Immunotherapies for the blockade of B7-H1 and its receptor PD-1 are currently in clinical trials for patients with advanced malignancies, and objective tumor regressions have been observed. Notably, preliminary results suggest that B7-H1 expression by tumor cells correlates with the likelihood of tumor regression following PD-1 blockade. To determine whether patients with Merkel cell carcinoma (MCC) would be candidates for this emerging class of immunotherapeutics, MCCs were studied for B7-H1 expression. The relationship between B7-H1 expression and tumor infiltrating immune cells, including macrophages and tumor infiltrating lymphocytes (TILs) was also studied.
Design: Cases of MCC were identified in the surgical pathology archives. B7-H1 immunohistochemistry was performed using mAb 5H1 on archived, paraffin-embedded tissue, and cases demonstrating more than 5% membranous expression by tumor or associated immune infiltrates were considered positive. The degree of TILs was scored as mild (rare), moderate (focal), or severe (diffuse).
Results: We found that 56% (14/25) cases of MCC demonstrated B7-H1 expression by tumor or geographically associated immune infiltrates (median cell expression=5%). 100% (14/14) of the positive cases were associated with at least mild TILs, compared to 0% (0/11) of B7-H1 negative cases (p<0.0001). In all (14/14) positive cases, B7-H1 expression was observed solely at the interface with TILs, suggesting an adaptive immune response of B7-H1 expression as a result of T-cell secreted cytokines such as IFN-gamma.
Conclusions: B7-H1 is a critical immune modulating component within the tumor microenvironment. Paradoxically, while the presence of TILs suggests on ongoing host response, TILs may actually trigger their own downregulation by secreting cytokines that lead to upregulation of B7-H1 by tumor and associated antigen presenting cells. These findings, in combination with the studies that suggest that B7-H1 expression by tumor may serve as a biomarker of response, indicate that PD-1/B7-H1 blockade should be further explored as a therapeutic option in patients with metastatic MCC.
Category: Dermatopathology

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 119, Tuesday Morning

 

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