Cancer Cells and the Tumor Microenvironment

Understanding the Tumor Microenvironment

Cancer cells engage extensively with their surrounding environment, known as the tumor microenvironment. This ecosystem comprises immune cells, blood vessels, and connective tissue that play pivotal roles in regulating tumor growth.

The Role of Immune Cells

Tumor-infiltrating immune cells can have varying effects on cancer progression, acting either as anti-tumor agents or promoting tumor growth. Notably, T cells, a specific type of immune cell, have been linked to improved health outcomes across various cancer types.

The Immunoscore in Colorectal Cancer

In colorectal cancer, the presence of T cells has led to the creation of the Immunoscore, a prognostic tool designed to predict the risk of cancer recurrence based on T cell invasion within tumor specimens. Generally, a higher presence of T cells in the tumor microenvironment correlates with better clinical outcomes.

Complexities of Immune Infiltration

However, recent findings published in the Journal of Clinical Investigation indicate that the relationship between immune cell infiltration and prognosis in colorectal cancer may be more intricate. Researchers from the City of Hope, an independent cancer research and treatment center in California, discovered a subset of colorectal cancer patients who, despite having high levels of T cells in their tumors, experienced poor outcomes.

Study Findings

These patients exhibited early relapse compared to those with minimal immune cell presence. “This study is the first report of immune infiltrated tumors with poor health outcomes and is counter to the standard belief in the field,” stated Peter P. Lee, Chair of the Department of Immuno-Oncology at City of Hope and senior author of the study.

Genetic Correlations and Immune Signatures

Using public genetic databases, the researchers linked the expression of immune genes in colorectal cancer to patient prognosis. This analysis identified a high-risk class of colorectal cancers characterized by elevated expression of CD8+ T cells and the immune checkpoint protein PD-L1. Further examination revealed an “immune overdrive” signature, marked by the upregulation of all major immune cell types and immune checkpoints in this specific subset of tumors.

The Role of Immune Checkpoints

Immune checkpoint molecules, including PD-L1, act as critical regulators of the immune system. In the context of cancer, these checkpoints serve to suppress immune responses and shield tumor cells from attack.

Implications for Immunotherapy

Patients identified in this high-risk demographic may be ideal candidates for immunotherapy drugs known as checkpoint inhibitors, which aim to 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,” advised Marwan Fakih, co-director of the Gastrointestinal Cancer Program at City of Hope and lead author of the study. He emphasized that continuing standard care for these patients could result in poor prognoses, and that insights from this research should be leveraged to enhance 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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