Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates.

Nature
Yannick SimoniEvan W Newell

Abstract

Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein-Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks o...Continue Reading

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Datasets Mentioned

BETA
GSE113590

Methods Mentioned

BETA
flow cytometry
PCA
surgical resection
exome sequencing
PCR
RNA-seq
peptide exchange

Software Mentioned

HTSanalyzeR
GATK
netMHC3
R script
DESeq2
featureCounts
ANNOVAR
R package
voom
stats

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