Dr Cecchini on the Efficacy of Neoadjuvant Chemotherapy in CRC Liver Metastases

“MSI-H tumors did not have high amounts of CD8-positive cells in their liver metastases, which is counter to what we would have expected given the immunogenic subtype of disease, really suggesting that if [patients] develop liver metastases, they’ve lost that favorable immune environment.”

Michael Cecchini, MD, an associate professor of medicine (medical oncology) at Yale School of Medicine; as well as the co-director of the Colorectal Program in the Center for Gastrointestinal (GI) Cancers, the medical oncology section lead for the National Accreditation Program for Rectal Cancer, the co-director of the GI Clinical Research Team, and a phase 1 investigator at Yale Cancer Center, discussed findings from a study evaluating the clinical significance of neoadjuvant chemotherapy on levels of tumor-infiltrating lymphocytes (TILs) in patients with colorectal cancer (CRC) with liver metastases.

Patients who have undergone resection of primary colon cancer tumors and have high levels of immune effector cells in their resected tumors have more effective immune systems and typically have better outcomes than those with lower immune effector cell levels, Cecchini began. However, limited knowledge is available regarding the prognostic role of immune effector cells in patients with CRC liver metastases, he said. Therefore, Cecchini and colleagues—led by Yasaman Rezaie, MD, of Yale School of Medicine—conducted a study comparing the clinicopathologic features and TIL subpopulations between matched cohorts of primary CRC tumors and CRC liver metastases.

Cecchini noted that the dataset collected from the patients included in the study was well clinically annotated, allowing the investigators to gain a high level of information about the clinical characteristics of the population. The study showed that, similarly to in primary CRC tumors, high levels of CD8-positive cells in the tumor microenvironment of resected liver metastases were associated with favorable overall survival outcomes, according to Cecchini. Furthermore, when microsatellite instability–high (MSI-H) tumors were compared with microsatellite-stable tumors, MSI-H liver metastasis tumors had low levels of CD8-positive cells, which was surprising given the immunogenic nature of this disease subtype, he explained. This finding indicates that patients with CRC who develop liver metastases lose the favorable immune environment in their metastases, he concluded.