TILs Linked to Reduced Intratumor Heterogeneity in Triple Negative Breast Cancer

A high level of tumor-infiltrating lymphocytes (TILs) is associated with reduced intratumor heterogeneity in triple negative breast cancer (TNBC), suggesting that strong immune response may lead to sculpting of the tumor and a near equilibrium, and thus a better prognosis, according to findings that will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS).¹

Tumors with increased TILs have better outcomes; this is particularly true of TNBC and HER2-positive breast cancers. It is unclear, however, whether a strong immune response or greater genomic instability and mutational burden lead to larger clonal heterogeneity. Researchers therefore evaluated the relationships of TILs and genomic heterogeneity in different breast cancer subtypes.

For the study, researchers used previously reported immune metagene expression data as measures of immune infiltration. They then compared somatic mutations, mutation count, neoantigen load, measures of clonal heterogeneity, and the distribution of mutations in 119 cancer genes and 12 cancer pathways between good and poor TNBC prognosis.

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 that good prognosis TNBC with high immune infiltration had a lower total mutation count (P = .021) and predicted neo-antigen count (P = .035). TNBC with low immune infiltration, which had greater clonal heterogeneity and mutation load, may signify the consequence of escape from immune surveillance.

Reference

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 (SABCS); December 6-10, 2016; San Antonio, TX.