Ten percent of colorectal cancer patients have a poor prognosis despite high immune cell infiltration of the tumour.
Cancer cells interact extensively with their surrounding environment. Termed the tumour ‘microenvironment’, this ecosystem consists of immune cells, blood vessels and connective tissue that regulate tumour growth. The role of tumour-infiltrating immune cells may be anti-tumour or tumour-promoting. However, the presence of a specific type of immune cell called T cells has been associated with improved health outcomes across multiple cancer types.
For colorectal cancer, this observation has led to the development of the Immunoscore, a prognostic tool that predicts risk of cancer recurrence based on the extent of T cell invasion in the tumour specimen. While more T cells in the tumour microenvironment generally indicates better clinical outcomes, new findings published in the Journal of Clinical Investigation suggest that the prognostic value of immune cell infiltration may be more complex in colorectal cancer.
Researchers from City of Hope, a California-based independent cancer research and treatment center, identified a subset of colorectal cancer patients with poor outcomes despite having high levels of T cells in their tumours. These patients all relapsed and the relapse event occurred earlier than for patients with little to no immune cells in their tumours.
“This study is the first report of immune infiltrated tumors with poor health outcomes and is counter to the standard belief in the field,” said Peter P. Lee, Chair of the Department of Immuno-Oncology at City of Hope and senior author of the study.
Using public genetic databases, the researchers correlated the expression of immune genes in colorectal cancer to patient prognosis. This revealed a high-risk class of colorectal cancers characterized by high gene expression of CD8+ T cells and the immune checkpoint protein, PD-L1. In fact, further gene analysis revealed an “immune overdrive” signature, in which all major immune cell types and immune checkpoints were upregulated in this subset of colorectal tumours.
Immune checkpoint molecules, including PD-L1, are key regulators of the immune system. In cancer, checkpoints serve as the ‘brakes’ that dampen the immune response and protect tumour cells. Individuals from this high-risk population may be good candidates for immunotherapy drugs called checkpoint inhibitors that help restore immune function and prevent cancer recurrence.
“Those in this subgroup who have high immune cell infiltration and a high immune-suppressive tumor microenvironment should be considered for enrollment in clinical trials that use immune checkpoint inhibitors,” said Marwan Fakih, co-director of the Gastrointestinal Cancer Program at City of Hope and lead author of the study. “If we continue to treat these patients with standard of care, they will continue to have a poor prognosis. We should use what we learned in this study to improve their chances of survival.”
Written by Cheryl Xia, HBMSc.
- Fakih, M. et al. Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome. Journal of Clinical Investigation 10.1172/JCI127046 (2019). doi:10.1172/JCI127046
- Letisia Marquez. Subgroup of colorectal cancer patients ID’d: Do poorly, could benefit from immunotherapy. EurekAlert!
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