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| Status |
Public on May 17, 2024 |
| Title |
Lack of TREM2 during anti-PD-1 therapy reprograms intestinal macrophages and microbiota to enhance tumor rejection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The gut microbiota and tumor-associated macrophages (TAM) impact anti-PD-1 checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor TREM2 attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 combined with TREM2 deficiency induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus (R. gnavus) in the gut microbiota. Gavage of wild-type mice with R. gnavus recapitulated enhancement of anti-PD-1-mediated tumor elimination occurring in the absence of TREM2. The intestinal proinflammatory environment coincided with expansion, increased circulation and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti-PD-1 checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.
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| Overall design |
We performed single-cell RNA sequencing on intestinal myeloid cells , as well as bulk RNA-seq on total colonic tissue, from WT and TREM2-deficient mice treated or not with anti-PD-1. We also performed single-cell RNA sequencing on tumor immune cells from WT mice treated or not with Ruminococcus gnavus.
Details for HTO Antibodies:
HTO: Barcode Sequence: Hashtagged sample
TotalSeq™-B0301 anti-mouse Hashtag 1 Antibody: ACCCACCAGTAAGAC: First biological sample harvasted from WT mice either treated or not with Ruminococcus gnavus gavage.
TotalSeq™-B0302 anti-mouse Hashtag 2 Antibody: GGTCGAGAGCATTCA: Second biological sample harvasted from WT mice either treated or not with Ruminococcus gnavus gavage.
TotalSeq™-B0303 anti-mouse Hashtag 3 Antibody: CTTGCCGCATGTCAT: Third biological sample harvasted from WT mice either treated or not with Ruminococcus gnavus gavage.
TotalSeq™-B0303 anti-mouse Hashtag 4 Antibody: AAAGCATTCTTCACG: Forth biological sample harvasted from WT mice either treated or not with Ruminococcus gnavus gavage.
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| Web link |
https://www.science.org/doi/10.1126/sciimmunol.adi5374#supplementary-materials
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| Contributor(s) |
Di Luccia B, Molgora M, Khantakova D, Colonna M |
| Citation(s) |
38758808 |
| |
| Submission date |
Mar 29, 2024 |
| Last update date |
May 18, 2024 |
| Contact name |
Marco Colonna |
| E-mail(s) |
mcolonna@wustl.edu
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| Organization name |
Washington University in St. Louis
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| Department |
Immunology&Pathology
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| Lab |
Marco Colonna
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| Street address |
660 S. Euclid Ave
|
| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA1093426 |
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