Tumor monocytes take a star turn in immunochemotherapy for esophageal cancer
Researchers led by Ludwig Oxford Director Xin Lu and alumnus Thomas Carroll reported in Cancer Cell in July that a relatively high number of monocytes in tumors is linked to better outcomes in esophageal cancer patients treated with a combination of chemotherapy and immunotherapy. Further, they found that combining measurements of tumor mutational burden along with monocyte content (TMC) better predicts treatment response than either measurement alone. The study also uncovered a novel T cell inflammation signature that could serve as a general indicator of potential responsiveness to immunotherapy. Xin, Thomas and their colleagues analyzed samples from a clinical trial launched in 2015 by Ludwig Oxford, in which 35 patients with inoperable esophageal adenocarcinoma received four weeks of immune checkpoint blockade therapy alone before undergoing 18 weeks of combination immunochemotherapy. The researchers performed single cell RNA sequencing (scRNA-seq) on 65,000 cells from a subset of the clinical trial patients to generate a detailed cellular atlas of all the cell types of the upper gastrointestinal tract. Biopsies from all patients underwent bulk RNA sequencing. The team used computational methods—deconvolution algorithms—to analyze both datasets to determine the proportion of different cell types in each biopsy. The researchers additionally confirmed that the link between high TMC and improved outcomes also holds for the most common forms of gastric cancer.