A Tc1- and Th1-T-lymphocyte-rich tumor microenvironment is a hallmark of MSI colorectal cancer.

Microsatellite instability is a strong predictor of response to immune checkpoint therapy and patient outcome in colorectal cancer. Although enrichment of distinct T-cell subpopulations has been determined to impact the response to immune checkpoint therapy and patient outcome, little is known about the underlying changes in the composition of the immune tumor microenvironment. To assess the density, composition, degree of functional marker expression, and spatial interplay of T-cell subpopulations, 79 microsatellite instable (MSI) and 1,045 microsatellite stable (MSS) colorectal cancers were analyzed.

Prognostic Impact and Spatial Interplay of Immune Cells in Urothelial Cancer.

Background And Objective: Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer.

Methods: A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis.

Loss of TROP2 and epithelial cell adhesion molecule expression is linked to grade progression in pTa but unrelated to disease outcome in pT2-4 urothelial bladder carcinomas.

Introduction: Trophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status.

BLEACH&STAIN 15-marker Multiplexed Imaging in 3,098 Human Carcinomas Reveals Six Major PD-L1-driven Immune Phenotypes with Distinct Spatial Orchestration.

Unlabelled: Multiplex fluorescence IHC (mfIHC) approaches were yet either limited to six markers or limited to a small tissue size that hampers translational studies on large tissue microarray cohorts. Here we have developed a BLEACH&STAIN mfIHC method that enabled the simultaneous analysis of 15 biomarkers (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, and CD31) in 3,098 tumor samples from 44 different carcinoma entities within one week. To facilitate automated immune checkpoint quantification on tumor and immune cells and study its spatial interplay an artificial intelligence-based framework incorporating 17 different deep-learning systems was established.