Showing papers by "Katy Milne published in 2012"

CD20+ Tumor-Infiltrating Lymphocytes Have an Atypical CD27− Memory Phenotype and Together with CD8+ T Cells Promote Favorable Prognosis in Ovarian Cancer

Abstract: Purpose: Tumor-infiltrating lymphocytes (TIL), in particular CD8 + T cells and CD20 + B cells, are strongly associated with survival in ovarian cancer and other carcinomas. Although CD8 + TIL can mediate direct cytolytic activity against tumors, the role of CD20 + TIL is poorly understood. Here, we investigate the possible contributions of CD20 + TIL to humoral and cellular tumor immunity. Experimental Design: Tumor and serum specimens were obtained from patients with high-grade serous ovarian cancer. CD8 + and CD20 + TIL were analyzed by immunohistochemistry and flow cytometry. Immunoglobulin molecules were evaluated by DNA sequencing. Serum autoantibody responses to the tumor antigens p53 and NY-ESO-1 were measured by ELISA. Results: The vast majority of CD20 + TIL were antigen experienced, as evidenced by class-switching, somatic hypermutation, and oligoclonality, yet they failed to express the canonical memory marker CD27. CD20 + TIL showed no correlation with serum autoantibodies to p53 or NY-ESO-1. Instead, they colocalized with activated CD8 + TIL and expressed markers of antigen presentation, including MHC class I, MHC class II, CD40, CD80, and CD86. The presence of both CD20 + and CD8 + TIL correlated with increased patient survival compared with CD8 + TIL alone. Conclusions: In high-grade serous ovarian tumors, CD20 + TIL have an antigen–experienced but atypical CD27 − memory B-cell phenotype. They are uncoupled from serum autoantibodies, express markers of antigen-presenting cells, and colocalize with CD8 + T cells. We propose that the association between CD20 + TIL and patient survival may reflect a supportive role in cytolytic immune responses. Clin Cancer Res; 18(12); 3281–92. ©2012 AACR .

Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes

Abstract: Background: The immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival. Methods: ALC values were collected from patient records ≥ 2 years before, during or after primary treatment for high-grade serous ovarian cancer (HGSC). Lymphocyte subsets were assessed in peripheral blood by flow cytometry. CD8+ and CD20+ TIL were assessed by immunohistochemistry. Results: Overall, patients had normal ALC values two or more years prior to diagnosis of HGSC. These values were not predictive of disease severity or survival upon subsequent development of HGSC. Rather, ALC declined upon development of HGSC in proportion to disease burden. This decline involved all lymphocyte subsets. ALC increased following surgery, remained stable during chemotherapy, but rarely recovered to pre-diagnostic levels. ALC values recorded at diagnosis did not correlate with CD8+ or CD20+ TIL but were associated with progressionfree survival. Conclusions: Patients with high intrinsic ALC values show no clinical or survival advantage upon subsequent development of HGSC. ALC values at diagnosis are prognostic due to an association with disease burden rather than TIL. Therapeutic enhancement of ALC may be necessary but not sufficient to improve survival in HGSC.

Supplementary Tables S1 and S2

Abstract: This is the version of the manuscript as accepted after peer-review but prior to any changes made during the proofing and publication process. It is made available under a Creative Commons Attribution Non-Commercial No Derivatives Licence.