High-dimensional immunotyping of tumors grown in obese and non-obese mice

Abstract

Obesity is a disease characterized by chronic low-grade systemic inflammation and has been causally linked to the development of 13 cancer types. Several studies have been undertaken to determine if tumors evolving in obese environments adapt differential interactions with immune cells and if this can be connected to disease outcome. Most of these studies have been limited to single cell lines and tumor models and analysis of limited immune cell populations. Given the multicellular complexity of the immune system and its dysregulation in obesity, we applied high-dimensional suspension mass cytometry to investigate how obesity affects tumor immunity. We used a 36-marker immune-focused mass cytometry panel to interrogate the immune landscape of orthotopic syngeneic mouse models of pancreatic and breast cancer. Unanchored batch correction was implemented to enable simultaneous analysis of tumor cohorts to uncover the immunotypes of each cancer model and reveal remarkably model-specific immune regulation. In the E0771 breast cancer model, we demonstrate an important link to obesity with an increase in two T cell suppressive cell types and a decrease in CD8 T-cells.

Single-cell profiling of low-stage endometrial cancers identifies low epithelial vimentin expression as a marker of recurrent disease

“…The range algorithm has been used as unanchored batch correction for mass cytometry data. 21 No association was found between median signal intensity of all markers per tumor and the patient inclusion year (Spearman correlation = 0.11, p = 0.53), indicating that results are not affected by storage time. In total, 36 samples were evaluated; six samples were represented by one image, 29 samples by two images and one sample by three images.…”

Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1

“…The CD45 + population, representing nucleated hematopoietic cells along with its precursors, of the FCS files (including standard internal control) from four batches were downloaded from Cytobank and imported into RStudio 2022.12.0+353 for batch correction using Cydar with ncdfFlow v.2.36.0 80 and flowCore v.2.2.0 81 as dependency packages. 82 , 83 Twenty-seven channels were scaled on a cofactor of 5 using arcsinh transformation. 84 Samples were analysed using FlowJo v10.2 CL (BD), using linear axes after batch correction.…”

Breast cancer microenvironment and obesity: challenges for therapy

“…In another study, obese breast cancer patients demonstrated lower total T cell infiltration within tumors prior to treatment compared to women with a healthy range BMI [ 189 ]. Decreased T cell infiltration in mammary tumors has also been observed in pre-clinical models [ 155 , 182 , 190 , 191 ], which may suggest reduced immunosurveillance in tumors under conditions of obesity. In a pre-clinical model, treatment of mammary tumor-bearing mice with 27-hydroxycholesterol resulted in fewer cytotoxic CD8 + T lymphocytes within the tumor microenvironment [ 192 ].…”