Abstract A27: Deep learning for analysis of tumor-lymphocyte interactions in pancreatic ductal adenocarcinoma
Authors: Kobayashi Soma , Le Han , Chrastecka Lucie , Gupta Rajarsi , Hou Le , Abousamra Shahira , Fassler Danielle , Shroyer Kenneth R. , Samaras Dimitris , Kurc Tahsin , Moffitt Richard A. , Saltz Joel H. 
Published: March 2020

The interaction of tumor, stroma, and immune cells in pancreatic ductal adenocarcinoma (PDAC) is complex and difficult to quantify in patient samples. Recently, deep learning algorithms have shown successes in identifying tumor and lymphocytes regions on whole-slide images derived from routinely collected histopathologic specimens. The Cancer Genome Atlas (TCGA) in particular has generated whole-slide images as well as paired molecular data, thus allowing for combined spatial and molecular analyses of tumor-lymphocyte interactions. We have previously highlighted this resource by computationally mapping tumor-infiltrating lymphocytes (TILs) on digital images across 13 tumor types. To achieve this, convolutional neural networks were trained on lymphocyte images annotated by expert pathologists and then used to detect spatial TIL patterns. This led to identification of four qualitative TIL pattern categories, which varied depending on tumor type as well as molecular immune subtype, demonstrating the potential of these spatial structures to provide further insights into tumor microenvironments and their relationship to overall survival. We have now extended this deep learning pipeline to include identification of tumor regions in PDAC, allowing study of TIL patterns in the context of their relative spatial localization to tumors. Using the deep learning algorithm to define the tumor region, we applied erosion and dilation operations to further capture the peritumoral region, the outer and inner regions of the tumor, as well as desmoplasia far from the tumor cells. We thus defined lymphocytes by their spatial localization as being internal, tumoral, peritumoral, or outer with these masks. We then used nearest-neighbor and density-based approaches to quantify TIL infiltration patterns with respect to tumor. These features vary significantly across the previously identified TIL patterns and may serve as additional parameters to define the microenvironment conditions in patient samples. Here we demonstrate that features extracted using our pipeline recapitulate canonical histologic properties. Using immune cell abundance estimates from gene expression generated by CIBERSORT, we find that samples with tumor TIL densities above median have more M1 macrophages, while those below median have more M2 macrophages. We also observe that slides with a higher peritumoral TIL density relative to tumoral TIL density have higher Treg fractions. Ongoing work on improving the resolution and cell specificity of our pipeline will allow us to ask more specific questions and permit higher granularity in linking clinical outcomes to spatial immune phenotypes.

Citation Format: Soma Kobayashi, Han Le, Lucie Chrastecka, Rajarsi Gupta, Le Hou, Shahira Abousamra, Danielle Fassler, Kenneth R. Shroyer, Dimitris Samaras, Tahsin Kurc, Richard A. Moffitt, Joel H. Saltz. Deep learning for analysis of tumor-lymphocyte interactions in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A27.