Multi-Cell Communities in the Tumour Microenvironment Impact Gastric Cancer Progression and Patient Outcomes

Wednesday - August 30 2023, 00:37 UTC - 1 year ago

A new study conducted by scientists at The University of Texas MD Anderson Cancer Center has uncovered new insight into the role of the tumour microenvironment in the progression of gastric cancer. The team used single-cell RNA sequencing to investigate the diverse immune and stromal cell populations present and identified six unique 'ecotypes'. Cells belonging to two of the 'ecotypes' (EC3 and EC6) were found to have distinct clinical characteristics, with patients with EC6 exhibiting more advanced stages of cancer and worse outcomes.

A recent study conducted by scientists at The University of Texas MD Anderson Cancer Center offers new insight into how the tumor microenvironment changes during the development of gastric cancer. Highlights of the study, published in Cancer Cell, include a connection between multicellular communities and patient outcomes, as well as a promising new target for therapy.

Gastric adenocarcinoma ranks among the deadliest cancers worldwide, primarily due to its natural resistance to treatment. However, the cellular and molecular processes that drive the transition from early pre-cancerous stages to tumor formation and metastasis remain largely unclear. This study illuminates the ways in which different immune and stromal cell subsets change throughout the progression of gastric cancer.

The study was conducted by Linghua Wang, M.D., Ph.D., associate professor of Genomic Medicine, in collaboration with Jaffer Ajani, M.D., professor of Gastrointestinal Medical Oncology, and Ruiping Wang, Ph.D., postdoctoral fellow in the Wang Lab. "Gastric adenocarcinoma exhibits a high degree of heterogeneity with respect to both its phenotypes and molecular characteristics, but research around it has lagged behind other cancer types," Wang said. "Most studies have concentrated on tumor cells and largely overlooked the immune and stromal cells within the tumor microenvironment, which are very dynamic and play critical roles in cancer progression. This study represents the largest single-cell RNA sequencing cohort of gastric adenocarcinoma to date and brings important new insights into how these cell populations impact disease progression." .

By obtaining single-cell RNA sequencing (scRNA-seq) data from 68 gastric adenocarcinoma samples encompassing various disease stages — including precancerous lesions, localized tumors, and distant metastases — along with normal tissue and peripheral blood samples, the team characterized the diverse immune and stromal cell populations within the tumor microenvironment and discovered exploitable targets to modulate the tumor microenvironment.

Various immune and stromal cell subsets formed multicellular communities, or collections of cell states, present in the tumor microenvironment of an individual tumor sample. The research team termed these groups "ecotypes" and identified six unique ecotypes, with each dominated by specific immune and stromal cell states.

"While many published single-cell studies have focused on characterizing the heterogeneity of each individual cell compartment, our study utilized a novel approach and concept of integrating various components of the tumor microenvironment to define ecotypes and investigated their clinical significance," Wang said. "This approach can readily be applied to studies in other cancer types." .

A notable discovery is that two ecotypes (EC3 and EC6) correlated with different histological, genomic, and clinical features of primary gastric adenocarcinomas. Tumors categorized as EC3 were composed mainly of immune cell subsets, whereas EC6 tumors predominantly included stromal cell subsets. Patients with EC6 tumors had more aggressive disease and significantly poorer survival outcomes than those with EC3.

TLDR: A new study conducted by scientists at The University of Texas MD Anderson Cancer Center has uncovered new insight into the role of the tumour microenvironment in the progression of gastric cancer. The team used single-cell RNA sequencing to investigate the diverse immune and stromal cell populations present and identified six unique 'ecotypes'. Cells belonging to two of the 'ecotypes' (EC3 and EC6) were found to have distinct clinical characteristics, with patients with EC6 exhibiting more advanced stages of cancer and worse outcomes.