SAN ANTONIO – A high level of tumor-infiltrating lymphocytes (TILs) is associated with reduced intratumor heterogeneity and improved prognosis in triple negative breast cancer (TNBC), a study presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) has shown.1
“TNBC with high TILs have better prognosis but it is not clear why TNBCs differ in TIL content,” said Thomas Karn, PhD, Department of Obstetrics and Gynecology, J. W. Goethe-University, Germany. “High mutation/antigen load may lead to a greater antitumor immune response.”
Immunoediting is the idea that the cancer and the immune system are in an “arms race” with either “tumor elimination” of a period of “equilibrium” which may be followed by tumor “immune escape.” Equilibrium allows for immune selection that may prune clonal diversity, while immune escape allows tumors that are “invisible” to, or have escaped. immune control to clonally diversify.
Therefore, researchers assess the relationship between immune gene expression and genomic complexity in TNBC. For the study, researchers assigned immune infiltration to 655 TCGA breast cancer samples through previously described immune metagenes and transferred immune signature to RNA-sequenced data, and applied those to 208 TCGA TNBC samples. Somatic mutation count, neoantigen load, clonal heterogeneity, and mutation in 119 canonical cancer genes were evaluated for correlation with immune infiltration.
Results showed a positive but weak correlation between mutation count and immune metagene expression in the overall cohort of breast cancer subtypes (P =.08), which was driven largely by the higher mutation count and immune infiltration in TNBC.
When researchers analyzed TNBC separately, they found that good prognosis TNBC with high immune infiltration had a lower total mutation count (P =.021) and predicted neoantigen count (P =.035).
“Good prognosis TNBC has low mutation and neoantigen loads,” noted Dr Karn.
TNBC with low immune infiltration, which had greater clonal heterogeneity and mutation load, may represent the result of immune escape.
“High immune gene expression is associated with better prognosis and lower intratumor heterogeneity in TNBC,” Dr Karn explained.
“These results suggest a near equilibrium between cancer and immune surveillance with immune pruning of clonal heterogeneity in immune-rich TNBC,” concluded Dr Karn. “TNBC with low immune infiltration has greater clonal heterogeneity and higher mutation load, suggesting escape from immune surveillance and clonal diversification.”
1. Karn T, Jiang T, Hatzis C, et al. Immune sculpting of the triple negative breast cancer genome. Paper presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX.