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T cells expressing modified Fc receptor infiltrate solid tumors and provide long-term anti-tumor protection

GSE263177 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2024/12/01 Platform GPL18573
At a glance

RNA-seq (gene expression) · human · 24 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
24 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
The clinical success of T cells armed with chimeric antigen receptor (CAR-T) to cure patients with hematological malignancies, has demonstrated the immense therapeutic potential of equipping T cells with synthetic receptors. Nonetheless, the scarcity of tumor-specific antigens and the limited capacity of T cells to infiltrate the tumor microenvironment significantly limit its clinical use in solid tumors.
Read the full summary ↓
Here, we provide evidence of FcγRI expressing CD8+ T cells presence in both mouse and human tumors as well as inflammation sites. Inspired by this discovery, we engineered a novel FcγRI-based receptor for T cells. This design allows T cells to target tumor cells indirectly through antibody intermediates, separating the processes of antigen recognition and T cell activation. This approach allows T cells to initiate killing exclusively against cells with antigen overexpression, thus minimizing on-target off-tumor cytotoxicity. Interestingly, the modified FcγRI expression in T cells unexpectedly induces constitutive expression of the CD11b integrin. This additional effect enables the engineered T cells to efficiently infiltrate the tumor basement membrane and develop an effector memory phenotype, potentially promoting long-term anti-tumor activity. The presence of these effector memory subsets characterized complete responders and mediated tumor regression upon rechallenge. Overall, T cell-mediated ADCC suggests an alternative, novel strategy for conventional CAR-T cell design, enables T cells to differentiate between target cells expressing the same antigen, and overcomes the physical barriers of the tumor microenvironment.
This dataset
Open GSE263177 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE263177_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1096041 and SRA study SRP499616. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly in triplicate
Not activated AG2G transduced T cells ×3 Sub-optimally activated AG2G transduced T cel… ×3 Optimally activated AG2G transduced T cells ×3 Not activated Sham transduced T cells ×3 Sub-optimally activated Sham transduced T cel… ×3 Optimally activated Sham transduced T cells ×3 Not activated CAR Her2 transduced T cells ×3 Optimally activated CAR Her2 transduced T cel… ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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