The complex microenvironment characteristic of pancreatic ductal adenocarcinoma (PDAC) has been implicated as a critical mediator of tumor progression and therapeutic response. Spatial relationships of individual cellular and acellular components within tumors may offer novel insights into the dynamic and complex functions of PDAC. Using eight-color multiplex immunohistochemistry and novel spatial analysis algorithms, we report a heterogeneous and increased population of infiltrating T lymphocytes in the tumors compared to uninvolved pancreatic tissues of treatment-naïve PDAC patients. Spatial distribution of cytotoxic T cells in proximity to cancer cells independently correlates with increased overall patient survival. Collagen-I and aSMA-positive fibroblasts do not correlate with a paucity of T-cell accumulation around cancer cells, suggesting that PDAC desmoplasia may not be a simple physical barrier. However, T-cell infiltration was reduced in proximity to specific cancer cell subpopulations, supporting cancer-cell intrinsic mechanisms for immune avoidance. Further expansion of this technology using early and late primary tumors and metastatic tissue of genetically engineered mouse models (KrasLSL-G12D; p53R172H; PDX1-Cre; EYFPLSL) demonstrates similar T-cell heterogeneity and spatial associations. These data support the validity of multiplex and spatial analysis platforms for exploring the structure-function relationships in the PDAC microenvironment and suggest differential spatial relationships between cancer subtypes and the surrounding microenvironment may be a determining factor in PDAC progression.
This abstract is also being presented as Poster A04.
Citation Format: Julienne L. Carstens, Pedro Correa de Sampaio, Soutik Barua, Huamin Wang, Jared K. Burks, Arvind Rao, Valerie S. LeBleu, Raghu Kalluri. Intratumoral T-cell distribution in murine and patient pancreatic cancer correlates with tissue heterogeneity and survival [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 PR08.