Abstract
CD8 T cell is an essential component of tumor-infiltrating lymphocytes (TIL) and tumor immune microenvironment (TIME). Using the xCell CD8 T cell score of whole tumor gene expression data, we estimated these cells in total of 3837 breast cancer patients from TCGA, METABRIC and various GEO cohorts. The CD8 score correlated strongly with expression of CD8 genes. The score was highest for triple-negative breast cancer (TNBC), and a high score was associated with high tumor immune cytolytic activity and better survival in TNBC but not other breast cancer subtypes. In TNBC, tumors with a high CD8 score had enriched expression of interferon (IFN)-α and IFN-γ response and allograft rejection gene sets, and greater infiltration of anti-cancerous immune cells. The score strongly correlated with CD4 memory T cells in TNBC, and tumors with both a high CD8 score and high CD4 memory T cell abundance had significantly better survival. Finally, a high CD8 score was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, a high CD8 T cell score is associated with better survival in TNBC, particularly when tumor CD4 memory T cells were elevated. Our findings also suggest a possible use of the score as a predictive biomarker for response to immune checkpoint therapy.
Highlights
The tumor immune microenvironment (TIME) plays a critical role in tumor progression, response to therapeutics, and prognosis in several cancers [1], including breast cancer [2,3]
Loi et al showed that Tumor-infiltrating lymphocytes (TIL) was associated with reduced risk of death in 2009 triple-negative breast cancer (TNBC) patients [5], and Denkert et al showed a positive association between TILs and response to neoadjuvant chemotherapy (NAC), including the achievement of pathological complete response (pCR) in TNBC, in 1000 breast cancer patients [9]
To establish the accuracy of this scoring method, we examined if the CD8 T cell score correlates with expression of the CD8 T cell surface marker genes, CD8A and CD8B
Summary
The tumor immune microenvironment (TIME) plays a critical role in tumor progression, response to therapeutics, and prognosis in several cancers [1], including breast cancer [2,3]. Tumor-infiltrating lymphocytes (TIL) are one of the major components of TIME, and the density and types of lymphocytes in the TIL fraction of a tumor have marked prognostic associations in breast cancer [4,5]. This is the case for triple-negative breast cancer (TNBC), which has the greatest number of TILs [3,5]. TIL has been reported as a prognostic indicator and a predictive biomarker for pathological complete response (pCR) following neoadjuvant chemotherapy (NAC), which is considered an important surrogate to predict the long-term clinical outcome for TNBC patients [5,8]. Another study has reported similar results [10]
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