Immune Cell Infiltration Impacts Chemotherapy Efficacy in B-NHL

作者：Peter‐Martin Bruch, Christina Schniederjohann, Harald Voehringer, Matthias Meyer-Bender, Sarah Koziel, Lisa-Maria Held, Erin Chung, Hilka Rauert‐Wunderlich, Marita Ziepert, Norbert Gattermann, Gerhard Held, German Ott, Andreas Rosenwald, Wolfgang Huber, Sascha Dietrich · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-209562 · 研究领域：Chronic Lymphocytic Leukemia Research、Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction

Introduction Microenvironmental profiling in lymphoma has identified clinically relevant subgroups through transcriptional and genomic profiling. We further enhance the characterization of DLBCL by examining the variations in cellular composition and spatial architecture and correlating these findings with clinical outcomes following chemoimmunotherapy. Method Using CO-Detection by indEXing (CODEX) we characterized the cellular composition of aggressive B-cell non-Hodgkin lymphoma samples from 193 patients at initial diagnosis which were consecutively treated with chemoimmunotherapy in the RICOVER-60 trial (NCT00052936), one of the landmark studies establishing R-CHOP as the standard treatment for DLBCL. Samples were assembled in tissue microarrays and stained with 54-plex antibody panel targeting microenvironmental cells along with important functional markers of malignant B cells. Genetic and clinical annotations were integrated to represent known tumor cell intrinsic features. Results Our analysis revealed that the cellular composition of the microenvironment in diffuse large B-cell lymphoma (DLBCL) varied significantly among samples but remained consistent between technical replicates. This heterogeneity was observed across all major non-lymphoma cell types: T cells ranged from 0.7% to 85% of all cells, with a mean frequency of 29%, followed by tumor-associated macrophages (5%), stromal cells (4%), dendritic cells (2%), and other myeloid cells (4%). We further focused on ...