Summary
The anti‐tumor immune response is considered to be due to the T‐cell receptor (TCR) binding to tumor antigens, which can be either wild‐type, early stem cell proteins, presumably foreign to a developed immune system; or mutant peptides, foreign to the immune system because of a mutant amino acid (aa) or otherwise somatically altered aa sequence. Recently, very large numbers of TCR complementarity‐determining region‐3 (CDR3) aa sequences obtained from tumor specimens have become available. We developed a novel algorithm for assessing the complementarity of tumor mutant peptides and TCR CDR3s, based on the retrieval of TCR CDR3 aa sequences from both tumor specimen and patient blood exomes and by using an automated process of assessing CDR3 and mutant aa electrical charges. Results indicated many instances where high electrostatic complementarity was associated with a higher survival rate. In particular, our approach led to the identification of specific genes contributing significantly to the complementary, TCR CDR3‐mutant aa. These results suggest a novel approach to tumor immunoscoring and may lead to the identification of high‐priority neo‐antigen, peptide vaccines; or to the identification of ex vivo stimulants of tumor‐infiltrating lymphocytes.
It became apparent several years ago that RNAseq and exome files prepared from tissue could be mined for adaptive immune receptor (IR) recombinations, which has given extra value to datasets originally intended for gene expression or mutation studies. For example, recovery of IR recombination reads from tumour specimen genomics files can correlate with survival rates. In particular, many benchmarking processes have been applied to the two sets of the IR recombination reads obtained from the cancer genome atlas files, but these two sets have never been directly compared.Here we show that both sets largely agree regarding several parameters. For example, recovery of TRB recombination reads from both WXS and RNAseq files representing metastatic melanoma was associated with a better outcome (p < .0004 in both cases); and T-cell receptor recombination read recovery, for both genomics file types, associated very strongly with T-cell gene expression markers. However, the use of CDR3 chemical features for survival distinctions was not consistent. This topic, and the surprising result that both datasets indicated that primary melanoma with recovery of IR recombination reads, in stark contrast to metastatic melanoma, represents a worse outcome, are discussed.
Highlights
Establishment of an immunological distinction between endometrioid and serous uterine cancers.
High priority CDR3s, mutant amino acids (AA) for endometrioid cancer prognosis, therapy tools.
Further understanding of CDR3-mutant AA complementarity scoring factors, such as HLA binding.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.