JAMMIT Analysis Defines 2 Semi-Independent Immune Processes Common to 29 Solid Tumors

Abstract

Immunophenotype of solid tumors has relevance to cancer immunotherapy, as not all patients respond optimally to treatment utilizing monoclonal antibodies. Bioinformatic studies have failed to clearly identify tumor immunophenotype in a way that encompasses a wide variety of tumor types and highlights fundamental differences among them, complicating prediction of patient clinical response. The novel JAMMIT algorithm was used to analyze mRNA data for 33 cancer types in The Cancer Genome Atlas (TCGA). We found that B cells and T cells constitute the principal source of variation in most patient cohorts, and that virtually all solid malignancies formed three hierarchical clustering patterns with similar molecular features. The second main source of variability in transcriptomic studies we attribute to monocytes. We identified the three tumor types as TC1-mediated, TC17-mediated and non-immunogenic immunophenotypes and used a 3-gene signature to approximate infiltration by agranulocytes. Methods of in silico validation such as pathway analysis, Cibersort and published data from treated cohorts were used to substantiate these findings. Monocytic infiltrate is found to be related to patient survival according to immunophenotype, important differences in some solid tumors are identified and deficiencies of common bioinformatic approaches relevant to diagnosis are detailed by this work.