GEO series
PD-1 is induced on tumor-associated macrophages in obesity to directly restrain anti-tumor immunity
GSE242839
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
29 samples
Submitted 2024/07/19
Platform GPL24247Platform GPL24676
Summary
Obesity is a leading risk factor for progression and metastasis of many cancers1,2, yet can also promote improved survival for some cancers3-5 and enhance responses to some immune checkpoint blockade therapies6-8. The role of the immune system in the obesity-cancer connection and how obesity influences immunotherapy, however, remain unclear. While PD-1 expression by macrophages has been described9-12, we found that obesity selectively induced PD-1 on macrophages and that PD-1 directly impaired macrophage function. Single cell RNA sequencing of murine colorectal carcinoma tumors showed obesity remodeled myeloid and T cell populations, with fewer clonally expanded effector T cells and increased abundance of PD-1+ tumor-associated macrophages (TAM). Cytokines and molecules associated with obesity, including IL-6, leptin, and insulin, and the unsaturated fatty acid palmitate, induced PD-1 expression on macrophages in a glycolysis-dependent manner and that MTORC1 pathway signaling is essential for PD1 expression. PD-1+ TAMs had increased mitochondrial respiration, fatty acid metabolism and cell cylewhile PD-1- TAMs had increased inflammatory signature , phagocytosis and antigen presentation to T cells. These patterns were directly regulated by PD-1, as recombinant PD-L1 reduced macrophage glycolysis, phagocytic capacity and antigen presentation, and this was reversed with blocking PD-1 antibody. Further, inhibition of glycolysis with 2-deoxyglucose prevented the increase in CD86, MHC-I and MHC-II that would otherwise occur with anti-PD-1 treatment. Conversely, PD-1-deficient Pdcd1-/- TAMs had high rates of glycolysis, phagocytosis, and expression of MHC-II. Myeloid-specific PD-1 deficiency correlated with slower tumor growth, enhanced TAM antigen presentation capability, and increased CD8 T cell activation together with reduced markers of exhaustion. These findings show metabolic signaling and type 1 inflammatory cues in obesity induces PD-1-mediated suppression of TAM function and reveal a unique macrophage-specific and glycolysis-dependent mechanism to modulate immune tumor surveillance and checkpoint blockade. This may contribute to increased cancer risk yet improved response to PD-1 blockade in TAM-enriched tumors and obesity.
Published in
Bader JE, Wolf MM, Lupica-Tondo GL et al.
· Nature 2024
· PMID 38867043
· doi:10.1038/s41586-024-07529-3
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE242839_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 29 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1015132 and SRA study SRP459649. Searching any of these in the dataset finder brings you back here.
Study design
24 conditions, each sampled once — no replicated groups
MC38 TAM IgG ×3
MC38 TAM aPD1 ×3
healthy dono ×2
Read from 29 sample titles: 24 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7771840 MC38 TAM IgG 1
- GSM7771841 MC38 TAM IgG 2
- GSM7771842 MC38 TAM IgG 3
- GSM7771843 MC38 TAM aPD1 1
- GSM7771844 MC38 TAM aPD1 2
- GSM7771845 MC38 TAM aPD1 3
- GSM7771846 TAM 1 lo
- GSM7771847 TAM 2 lo
- GSM7771848 TAM 3 lo
- GSM7771849 TAM 4 lo
- GSM7771850 TAM 5 lo
- GSM7771851 TAM 1 hi
- GSM7771852 TAM 2 hi
- GSM7771853 TAM 3 hi
- GSM7771854 TAM 4 hi
- GSM7771855 TAM 5 hi
- GSM7771856 TAM 6 lo
- GSM7771857 TAM 7 lo
- GSM7771858 TAM 8 lo
- GSM7771859 TAM 9 lo
- GSM7771860 TAM 10 lo
- GSM7771861 TAM 6 hi
- GSM7771862 TAM 7 hi
- GSM7771863 TAM 8 hi
- GSM7771864 TAM 9 hi
- GSM7771865 TAM 10 hi
- GSM7771866 healthy donor 1
- GSM7771867 healthy donor 2
- GSM7771868 PTEN Haplo
Similar datasets
- GSE281472 Targeting CD206+ macrophages disrupts the establishment of a key anti-tumor immune axis 245 samples
- GSE264145 Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer 12 samples
- GSE310025 Intrinsic RB activation induces tumoral and stromal anti-tumor responses that limit triple-negative breast cancer [RNA-Seq] 28 samples
- GSE342640 Insulin resistance is associated with mammary mitochondrial dysfunction at the onset of human lactation 159 samples
- GSE324329 A kidney-protective mechanism via cellular oxidative stress reduction induced by CD5L protein 38 samples
- GSE294216 Resistance to the KRASG12D Inhibitor MRTX1133 is Associated with Aberrant Histone Acetylation and Increased Sensitivity to BET Inhibition 36 samples
- GSE288077 Metabolic dysfunction-associated steatotic liver disease may increase intrahepatic interferon gene signatures in patients with chronic hepatitis B 35 samples
- GSE315101 Soluble DLK1 secreted by telomere-shortening-induced senescent microglia impairs oligodendrocyte functions and alters neuronal activity [DLK1_snRNA-seq] 27 samples
Share this dataset
Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.