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| Status |
Public on Feb 05, 2024 |
| Title |
Response to tumor- infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+T- myeloid cell networks in melanoma [CD45 scRNAseq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell–intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor–reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network–based biomarkers that could improve patient selection and guide the design of ACT clinical trials.
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| |
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| Overall design |
Melanoma tumor gene expression profiling pre and post TIL adoptive cell therapy by CD45-sorted single cell RNAseq
|
| Web link |
https://www.science.org/doi/10.1126/sciimmunol.adg7995
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| |
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| Contributor(s) |
Barras D, Harari A, Dangaj D, Coukos G |
| Citation(s) |
38306416 |
| Submission date |
Dec 21, 2022 |
| Last update date |
Feb 06, 2024 |
| Contact name |
David Barras |
| E-mail(s) |
david.barras@chuv.ch
|
| Organization name |
Centre hospitalier universitaire vaudois
|
| Department |
Oncology
|
| Street address |
AGORA, Bugnon 25A
|
| City |
Lausanne |
| State/province |
Vaud |
| ZIP/Postal code |
1005 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE222448 |
Response to tumor- infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+T- myeloid cell networks in melanoma |
|
| Relations |
| BioProject |
PRJNA914772 |
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