Variability in immune infiltrates and HLA expression in cholangiocarcinoma.

Abstract

230 Background: Cholangiocarcinoma continues to have a dismal prognosis. The lack of effective therapy prompted us to determine whether patients develop an immune response against their own tumors. The aim of this study is to evaluate the CD8 infiltrate and expression of HLA class I antigen processing machinery (APM) components in cholangiocarcinoma. The HLA class I antigen processing machinery (APM) components play a crucial role in expression of HLA class I tumor antigen derived peptide complexes. These complexes mediate the recognition of tumor cells by cognate T cells. Defects in the expression of HLA class I APM components by tumor cells suggests that the infiltrating lymphocytes impose selective pressure on tumor cells. This selective pressure would facilitate the outgrowth of tumors by escaping T cell recognition. Methods: Retrospective review of clinicopathologic factors was performed for 18 peripheral cholangiocarcinomas. Formalin fixed, paraffin embedded tumors were evaluated for the content of lymphocyte infiltrates and for the expression of HLA class I APM components. Results: Eighteen patients underwent a partial hepatectomy for peripheral cholangiocarcinoma of whom 10 were female. Median age was 63yo. The majority of patients had node negative tumors (10/12). All tumors had lymphocytic infiltration. Median number of lymphocytes in the fibrous septae between tumor lobules was 42 CD8 T cells per 10 high power field, but only 4 CD8 T cells within tumor lobules. HLA class I APM components was defective and not detected in three tumors, all of which were poorly differentiated. HLA expression was down regulated in 9 tumors. HLA expression was in normal range in the remaining 6 tumors. Median overall survival has not been reached. Conclusions: Lymphocytic infiltrates were seen in all resected cholangiocarcinoma specimens. The loss of HLA class I APM component expression in cholangiocarcinoma suggests that infiltrating lymphocytes reflect a patient’s immune response to his/her tumor. This information provides a sound rationale to consider immunotherapy in the treatment of cholangiocarcinoma, specifically with antibodies to check point molecules which enhance patients’ immune response against his own tumors.