|
| Status |
Public on Jan 11, 2022 |
| Title |
Physical interaction with antigen presenting cells primes a T helper tumor lineage |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cellular interactions in the tumor microenvironment (TME) drive T cell effector function, or dysfunction, and define a primary mechanism to target anti-tumor T cell immunity. Currently, the interactions that shape T cell function in the TME remain poorly understood. Here, we mapped the molecular programs of T and antigen-presenting cell interactions in human early non-small cell lung carcinoma lesions by physically interacting cell (PIC) sequencing. PIC-seq and imaging identified that in the TME, but not normal lung, PICs are enriched in clonally expanded CD4+PD-1+CXCL13+ T cells, expressing a unique combination of checkpoint molecules, transcription-factors, and cytokines, defining a novel T helper tumor-specific (Tht) program, conserved across cancer types. In vitro and in vivo genetic models of antigen specificity confirmed that the Tht prevalence in TME PICs is driven by tumor-antigen presentation of dendritic cells. Our study highlights CD4+ T-dendritic cell physical interaction as a key factor regulating the TME.
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| |
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| Overall design |
Transcriptional profiling of thousands of single cells and doublets (PIC) of interacting T and dendritic cells from both human tumors and mouse tumor models
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| Contributor(s) |
Amit I, Merad M, Tanay A, Cohen M, Giladi A, Hamon P, Li B, Barboy O, Zada M |
| Citation(s) |
35241835 |
| |
| Submission date |
Nov 05, 2020 |
| Last update date |
Apr 12, 2022 |
| Contact name |
Ido Amit |
| E-mail(s) |
ido.amit@weizmann.ac.il
|
| Phone |
972-8-9343338
|
| Organization name |
Weizmann Institute of Science
|
| Department |
Immunology
|
| Street address |
234 Herzl st.
|
| City |
Rehovot |
| ZIP/Postal code |
760001 |
| Country |
Israel |
| |
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| Platforms (4)
|
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (268)
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| Relations |
| BioProject |
PRJNA674818 |
| SRA |
SRP291299 |
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