Abstract B029: Mapping the vascular walls of colorectal cancer
Authors: Huang( 黄 ) Linglong(凌龙) , Herrera Mercedes , Sjölund Jonas , Chocoloff Vladimir , Joost Simon , Tabiev Rasul M. , Leiss Lina Wik , Strell Carina , Nunes Luis , Mezheyeuski Artur , Edler David , Martling Anna , Pontén Fredrik , Glimelius Bengt , Sjöblom Tobias , Kasper Maria , Pietras Kristian , Östman Arne 
Published: November 2024

Abstract
Introduction: Properties of tumor angiogenesis impact on tumor growth and composition of the tumor microenvironment. Tumor vessels are composed of pericytes and other mural cells. Detailed characterization of the cellular composition of the microvasculature can suggest functional vessel and case properties relevant for outcome, response to treatment and immune surveillance. Results: Based on single cell RNA-seq from three human stage II/III colon cancers and pilot in-situ multi-antibody staining of six tumors two main clusters of perivascular cells were identified; B1 (MCAM+, MYH11-) and B2 (MCAM+, MYH11+) cells. B1 cells displayed pericyte features including expression of RGS5, whereas B2 cells showed high expression of smooth muscle cell markers like ACTG2 and Desmin. Desmin-high B2 cells were predominantly located in muscular layers, whereas Desmin-low/MYH11-high B2 cells showed perivascular enrichment. An extended novel analyses workflow of digital image analysis was used to profile peri-endothelial composition in 19 intervals; 11 1-µm intervals from 0 to 10 µm and 8 5-µm intervals from 10 to 50 µm from endothelial areas. Each of these expansion areas was quantitated regarding density of PDGFRB+/- cells including B1/B2 cells, and a MYH11+/MCAM- cells. Density of macrophage subsets (CD68-positive subsets defined by CD163 and CD11c) were also quantitated. In general, B1 cells showed stronger spatial association with endothelial cells than B2 cells, and this spatial association was stronger for the PDGFRB+ B1 subset. Survival analysis indicated that prognostic relevance was strongest when PDGFRB+ (favorable prognosis) cells were closest to endothelial cells. Regarding perivascular macrophage density, M0 and transit M1/M2 macrophages were predominantly enriched in the peri-endothelial regions, whereas density of M1 and M2 increased gradually as distance from vessels increased. M2 density was overall associated with poor prognosis, whereas high density of other macrophage subsets overall was associated with good prognosis. Ongoing studies are using a clustering-based approach to identify vessel subsets, and prognosis associations are being consolidated in additional cohorts. Summary: This study provides a novel approach for high resolution profiling of perivascular status in CRC, and possibly other tumor types, that could be of specific importance to identify tumor features associated with response to angiogenesis-directed therapies.
Citation Format: Linglong( 凌 龙 ) Huang( 黄 ), Mercedes Herrera, Jonas Sjölund, Vladimir Chocoloff, Simon Joost, Rasul M. Tabiev, Lina Wik Leiss, Carina Strell, Luis Nunes, Artur Mezheyeuski, David Edler, Anna Martling, Fredrik Pontén, Bengt Glimelius, Tobias Sjöblom, Maria Kasper, Kristian Pietras, Arne Östman. Mapping the vascular walls of colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B029.