Journal: The Journal of Clinical Investigation

Article Title: A CD138 + tumor-associated macrophage/Siglec-F + neutrophil feed-forward loop promotes immune evasion in pancreatic cancer

doi: 10.1172/JCI199516

Figure Lengend Snippet: ( A ) Experimental design employed to evaluate the therapeutic efficacy of anti–IL-34 antibodies in conjunction with anti–PD-1 antibodies in PDAC. ( B ) Quantification of tumor weight ( n = 8 per group). ( C and D ) Quantification of Ki67 + cell counts ( C ) and the percentage of CC3 + area ( D ) per ×40 field in tumor sections ( n = 8 per group). ( E ) Overall survival probabilities of mice ( n = 8 per group). The dashed line indicates the time point when the combination therapy commenced. ( F and I ) Flow cytometry images showing CD138 + F4/80 + ( F ) and SAA3 + CXCL1 + ( I ) macrophages in the tumor tissues of mice following anti–IL-34 antibody treatment. ( G and H ) Quantification of data from F ( n = 6 per group). ( J and K ) Quantification of data from I ( n = 6 per group). ( L ) Representative plots illustrating the presence of Siglec-F + neutrophils in the tumor tissues of mice upon treatment with anti–IL-34 antibodies. ( M and N ) Quantification of data from L ( n = 6 per group). ( O ) Quantification of the frequencies of effector cell subsets among CD45 + cells in tumor tissues ( n = 6 per group). ( P and R ) Representative images depicting CD44 + CD62L – effector ( P ) and TIM3 + SLAMF6 – PD-1 + late-exhausted ( R ) CD8 + T cells within the tumor tissues. ( Q ) Quantification of data from P ( n = 6 per group). ( S ) Quantification of data from R ( n = 6 per group). ( T ) Overall survival probabilities of mice ( n = 8 per group). The dashed line indicates the time point when the combination therapy commenced. * P < 0.05, ** P < 0.01, and *** P < 0.001 by Kruskal-Wallis test with Dunn’s multiple-comparison test ( B – D , O , Q , and S ), by log-rank analysis ( E and T ), and by unpaired 2-tailed Student’s t test ( G , H , J , K , M , and N ). Data represent mean ± SEM.

Article Snippet: Mice were intraperitoneally injected with 200 μg of anti–IL-34 antibody (catalog MAB5195, R&D Systems) every other day, totaling 6 doses, starting on day 9 after the orthotopic inoculation of 5 × 10 5 KPC cells.

Techniques: Drug discovery, Flow Cytometry, Comparison

Journal: medRxiv

Article Title: Defining and Modeling Human Interleukin-34 Deficiency

doi: 10.64898/2026.02.21.26346696

Figure Lengend Snippet: (A) Standardized IL-34 levels measured in cerebrospinal fluid (CSF; SomaScan) across Y213X genotypes (WT/WT, WT/MUT, MUT/MUT). (B) Standardized IL-34 levels measured in serum (Olink) across Y213X genotypes. (C) Relationship between standardized IL-34 levels and age, shown for CSF (gray) and serum (red). (D) Correlation between serum and CSF IL-34 levels across all subjects. (E) Expected Y213X carrier and homozygote frequencies across populations and continents derived from allele frequency under Hardy–Weinberg equilibrium. (F) IL-34 levels in CSF and serum stratified by sex, dementia status, amyloid status, and tau status. (G) Pearson correlations between IL-34 and CSF Alzheimer’s disease biomarkers (Aβ 42 , pTau181, and total tau), shown for all subjects and after stratification by Y213X carrier status and amyloid status. Error bars denote 95% confidence intervals. Asterisks indicate significance thresholds (∗ p < 0.01, ∗∗ p < 0.001).

Article Snippet: Four mouse lines were used: APP swe , PSEN1 dE (APP/PS1) (The Jackson Laboratory, Bar Harbor, ME, USA, Stock No: 004462), IL-34 em2Smoc (Shanghai Model Organisms Center, Shanghai, China.

Techniques: Derivative Assay

Journal: medRxiv

Article Title: Defining and Modeling Human Interleukin-34 Deficiency

doi: 10.64898/2026.02.21.26346696

Figure Lengend Snippet: Box plots showing CSF IL-34 levels in individuals stratified by IL34 genotype (Y213/Y213, Y213/X, and X213/X213), measured across three independent experiments using two orthogonal proteomic platforms: two SomaScan assays (left and middle panels) and one Olink immunoassay (right panel). Across all platforms, carriers of the IL-34-Y213X variant show a marked reduction in CSF IL-34 levels. p values indicate statistical significance of genotype effects.

Article Snippet: Four mouse lines were used: APP swe , PSEN1 dE (APP/PS1) (The Jackson Laboratory, Bar Harbor, ME, USA, Stock No: 004462), IL-34 em2Smoc (Shanghai Model Organisms Center, Shanghai, China.

Techniques: Variant Assay

Journal: medRxiv

Article Title: Defining and Modeling Human Interleukin-34 Deficiency

doi: 10.64898/2026.02.21.26346696

Figure Lengend Snippet: (A) STRING protein–protein interaction network of proteins associated with CSF IL-34 levels, highlighting two major modules. (B) Gene Ontology enrichment results for the module positively associated with IL-34 (red network), showing enrichment for neuronal and synaptic biology. (C) Gene Ontology enrichment results for the module negatively associated with IL-34 (light orange network), enriched for cytokine-mediated signaling and related immune processes. Bubble size reflects gene counts and color reflects FDR-adjusted significance.

Article Snippet: Four mouse lines were used: APP swe , PSEN1 dE (APP/PS1) (The Jackson Laboratory, Bar Harbor, ME, USA, Stock No: 004462), IL-34 em2Smoc (Shanghai Model Organisms Center, Shanghai, China.

Techniques:

Journal: medRxiv

Article Title: Defining and Modeling Human Interleukin-34 Deficiency

doi: 10.64898/2026.02.21.26346696

Figure Lengend Snippet: (A) Volcano plot comparing CSF proteomes from IL-34 Y213X homozygotes and matched controls, highlighting nominally significant proteins. (B) Heatmap summarizing effect sizes and statistical significance for the selected proteins shown in panel A. (C) Functional enrichment of pathways represented among proteins decreased in IL-34 homozygotes. (D) Functional enrichment of pathways represented among proteins increased in IL-34 homozygotes. Bubble size reflects gene counts and color denotes FDR-adjusted significance.

Article Snippet: Four mouse lines were used: APP swe , PSEN1 dE (APP/PS1) (The Jackson Laboratory, Bar Harbor, ME, USA, Stock No: 004462), IL-34 em2Smoc (Shanghai Model Organisms Center, Shanghai, China.

Techniques: Functional Assay

Journal: medRxiv

Article Title: Defining and Modeling Human Interleukin-34 Deficiency

doi: 10.64898/2026.02.21.26346696

Figure Lengend Snippet: AlphaFold-predicted structure of IL-34 indicating the position of the Y213 residue and the resulting Y213X truncation. The truncation localizes to the unstructured C-terminal region, distal from the folded core of the protein, suggesting that the overall globular structure is preserved and that major disruption of somamer- or antibody-binding epitopes is unlikely.

Article Snippet: Four mouse lines were used: APP swe , PSEN1 dE (APP/PS1) (The Jackson Laboratory, Bar Harbor, ME, USA, Stock No: 004462), IL-34 em2Smoc (Shanghai Model Organisms Center, Shanghai, China.

Techniques: Residue, Disruption, Binding Assay