Publications

Cancers are conventionally classified as “hot” tumors that are associated with high tumor mutation burdens (TMBs) and tumor-infiltrating immune cells or “cold” tumors associated with a dearth of neoantigens and immune cell exclusion. This dichotomy is frequently used to define the degree of pre-existing immune cell reactivity within the tumor microenvironment and has been linked to clinical outcomes including the efficacy of immune checkpoint inhibitor (ICI) treatment. Recently, cancer-agnostic immune gene expression signatures (IGESs) denoting “hot” tumors, including the interferon-gamma (IFN-γ) and T cell-inflamed scores, have been derived from clinical cohorts as putative cancer-agnostic predictors of ICI treatment response in diverse cancer types. Whether TMB or ICI benefit is robustly associated with “hot” tumors defined by pre-existing immune characteristics across diverse cancer histologies remains ambiguous. Herein, we sought to address the following outstanding questions: (1) are IGESs used to identify “hot” and ICI-sensitive tumors associated with TMBs or long-term ICI responders across diverse cancer types; (2) similarly, is the composition of infiltrating immune cells agnostically associated with TMBs or long-term survivors after ICI; and lastly (3) do immune characteristics account for the variable response rates to ICIs across cancer types?