Abstract SY38-02: Immune-related changes in breast tumor evolution

Abstract

Abstract Increasing evidence supports a role for the immune system in tumor initiation and progression. Immune cells shape tumor evolution directly (e.g., anti-tumor immune response) and indirectly (e.g., changing the microenvironment) by selecting for cancer cells with certain properties. Immunotherapy is one of the most promising current therapeutic options and almost the only one that can effectively cure metastatic disease. However, thus far its success has been limited to a subset of patients. This may be a consequence of heterogeneity among tumors for mechanisms by which they escape immune surveillance. We hypothesized that the in situ to invasive carcinoma transition is a critical tumor progression step for immune escape in breast cancer that defines subsequent tumor evolution. This is due to the fact that in DCIS (ductal carcinoma in situ) cancer cells are still physically separated from the stroma by the basement membrane and myoepithelial cell layer, and tumor-infiltrating leukocytes are rarely detected in direct contact with cancer cells. In contrast, with invasive progression, cancer cells and leukocytes are intermingled, thus, only cancer cells that can survive in this environment will play a role in disease progression. To begin dissecting mechanisms of immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, DCIS, and invasive ductal carcinomas (IDC) by polychromatic FACS and found significant changes in multiple cell types. We also analyzed the gene expression profiles of T cells from each of these tissue types and found that T cells in DCIS are different from those in normal breast and invasive tumors. We validated some of these changes by multicolor immunofluorescence. We also performed high throughput sequencing of T cell receptor (TCR) of T cells in DCIS and found potential clonal expansions shared among patients. Lastly, we performed multicolor immunofluorescence analysis of checkpoint proteins in DCIS and IDC of different subtypes, and detected significant differences in expression patterns. Our results imply that analyzing immune-related changes during DCIS to IDC transition will identify novel targets for immunotherapy in breast cancer. Citation Format: Kornelia Polyak. Immune-related changes in breast tumor evolution. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY38-02.