Cancer cells interact extensively with their surrounding environment.
Termed the tumor ‘microenvironment’, this ecosystem consists of immune cells, blood vessels, and connective tissue that regulate tumor growth.
The role of tumor-infiltrating immune cells may be anti-tumor or tumor-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 the risk of cancer recurrence based on the extent of T cell invasion in the tumor specimen.
While more T cells in the tumor microenvironment generally indicate better clinical outcomes, 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 the 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 tumors.
These patients all relapsed and the relapse event occurred earlier than for patients with little to no immune cells in their tumors.
“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.
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 tumors.
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 tumor 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 the 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.”
References:
- 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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