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TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy
Di Luccia B, Molgora M, Khantakova D, Jaeger N, Chang HW, Czepielewski RS, Helmink BA, Onufer EJ et al.. Science immunology, 2024-05-17
Topic: Brain proteins, microglia and lab models
The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Di Luccia, B., Molgora, M., Khantakova, D., Jaeger, N., Chang, H. W., Czepielewski, R. S., et al. (2024). TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy. Science immunology. https://doi.org/10.1126/sciimmunol.adi5374
Vancouver
Di Luccia B, Molgora M, Khantakova D, Jaeger N, Chang HW, Czepielewski RS, et al. TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy. Science immunology. 2024. doi:10.1126/sciimmunol.adi5374. PMID: 38758808.
BibTeX
@article{diluccia2024-38758808,
author = {Di Luccia, B. and Molgora, M. and Khantakova, D. and Jaeger, N. and Chang, H. W. and Czepielewski, R. S. and Helmink, B. A. and Onufer, E. J. and others},
title = {{TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy}},
journal = {Science immunology},
year = {2024},
doi = {10.1126/sciimmunol.adi5374},
pmid = {38758808},
url = {https://doi.org/10.1126/sciimmunol.adi5374}
}
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Key findings
- Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1.
- Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota.
- Gavage of wild-type mice with R. gnavus enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2.
- A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4 + T cells to the tumor bed.
Why it matters
This study is about cancer immunotherapy in mice, not Alzheimer's disease. It found that TREM2 deficiency combined with anti-PD-1 treatment enhanced tumor elimination, which does not inform Alzheimer's treatment.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science immunology) |
| Journal's citation record | 2 / 4 | Science Immunology: journal h-index 164 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 54 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 8.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 3 / 4 | Cited 54 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Marco Colonna: h-index 172 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38758808) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Also tagged “macrophages”
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