Accession	GSE227054
Status	2023/4/1
Title	Cancer-specific CD8 T cell frequency at baseline in blood correlates with response to PD-1 blockade in Merkel cell carcinoma
Organism	Homo sapiens
Experiment type	Other
Summary	Understanding immunotherapy response and resistance is challenging due to difficulty identifying cancer-specific CD8 T cells. Merkel cell carcinoma (MCC) is typically driven by Merkel cell polyomavirus (MCPyV), facilitating identification of cancer-specific T cells across patients. We characterized cancer-specific T cells in 35 MCC patients, including from a neoadjuvant anti-PD-1 trial. Higher MCPyV-specific CD8 T-cell frequency in pre-treatment blood (but not tumors) correlated with response (p=0.0056). Single cell RNAseq revealed MCPyV-specific CD8 T cells in blood with increased stem/memory signatures and decreased exhaustion signatures relative to their intratumoral counterparts. Number of circulating cancer-specific T cells is likely most linked to primary response to immunotherapy as longitudinal samples documented emergence of additional resistance mechanisms, amidst abundant circulating cancer-specific CD8 T cells. These results suggest that blood acts as an important reservoir of cancer-specific CD8 T cells and suggests adoptive cell therapies may be particularly effective in patients without such cells.
Samples	GSM ID Sample info Characteristics Description GSM7090757 Expanded_TIL_Feature_barcodes_1A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:ADT Antibody or MHC multimer-derived oligonucleotide (ADT) GSM7090758 Expanded_TIL_Feature_barcodes_2A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:ADT Antibody or MHC multimer-derived oligonucleotide (ADT) GSM7090759 Expanded_TIL_Feature_barcodes_2B tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:ADT Antibody or MHC multimer-derived oligonucleotide (ADT) GSM7090760 Expanded_TIL_Feature_barcodes_3A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:ADT Antibody or MHC multimer-derived oligonucleotide (ADT) GSM7090761 Expanded_TIL_Feature_barcodes_3B tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:ADT Antibody or MHC multimer-derived oligonucleotide (ADT) GSM7090762 Expanded_TIL_Feature_barcodes_4A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:ADT Antibody or MHC multimer-derived oligonucleotide (ADT) GSM7090763 Expanded_TIL_Feature_barcodes_4B tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:ADT Antibody or MHC multimer-derived oligonucleotide (ADT) GSM7090764 Expanded_TIL_TCR_1A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:TCR V(D)J TCR library GSM7090765 Expanded_TIL_TCR_2A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:TCR V(D)J TCR library GSM7090766 Expanded_TIL_TCR_2B tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:TCR V(D)J TCR library GSM7090767 Expanded_TIL_TCR_3A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:TCR V(D)J TCR library GSM7090768 Expanded_TIL_TCR_3B tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:TCR V(D)J TCR library GSM7090769 Expanded_TIL_TCR_4A tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:TCR V(D)J TCR library GSM7090770 Expanded_TIL_TCR_4B tissue:Tumor; cell type:T cells expanded with phytohemagglutinin-purified mitogen, IL2 and IL15; library type:TCR V(D)J TCR library
Platform	GPL24676  : Illumina NovaSeq 6000 (Homo sapiens)
Literature	38340723