Antibody secreting plasma cells are made in response to a variety of pathogenic and commensal microbes. While all express core gene transcription program that allows them secrete large quantities immunoglobulin, unique transcriptional profiles linked expressing different antibody isotypes. IgA generally thought as short-lived mucosal tissues they have been understudied systemic sites like the bone marrow. We find IgA+ both small intestine lamina propria marrow long-lived transcriptionally...

The gut microbiome generates a diverse array of metabolites that actively shape host immunity, yet the pro-inflammatory potential microbial remains poorly understood. In this study, we identified hippuric acid, an aromatic microbe-derived metabolite, as potent enhancer responses using murine bacterial infection model and non-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics. Administering acid intraperitoneally in models Escherichia coli or LPS-induced...

The tumor suppressor

<p>Table S1 and Table S2</p>

<p>Figure S2 shows that the tumor microenvironment in both P47 and S47 mice is comprised of similar proportions subpopulations immune cells with phenotypes.</p>

<div>Abstract<p>The tumor suppressor TP53 is the most frequently mutated gene in cancer and mutationally inactivated fifty percent of sporadic tumors. Inactivating mutations also occur Li Fraumeni syndrome (LFS). In addition to germline LFS that completely inactivate this protein, there are many more mutant forms human populations partially protein: we call these inactivating “hypomorphs”. One hypomorphs a single nucleotide polymorphism (SNP) exists 6-10% Africans 1-2% African...

<p>Table S1 and Table S2</p>

<p>Figure S2 shows that the tumor microenvironment in both P47 and S47 mice is comprised of similar proportions subpopulations immune cells with phenotypes.</p>

<p>Figure S1 shows BMDMs from S47 mice are more anti-inflammatory and polarize towards a M2 phenotype following IL-4 stimulation.</p>

<div><p>The tumor suppressor <i>TP53</i> is the most frequently mutated gene in cancer and mutationally inactivated 50% of sporadic tumors. Inactivating mutations also occur Li Fraumeni syndrome (LFS). In addition to germline LFS that completely inactivate this protein, there are many more mutant forms human populations partially protein: we call these inactivating “hypomorphs.” One hypomorphs a SNP exists 6%–10% Africans 1%–2% African Americans, which changes proline...

<p>Figure S1 shows BMDMs from S47 mice are more anti-inflammatory and polarize towards a M2 phenotype following IL-4 stimulation.</p>

<p>Figure S1 shows BMDMs from S47 mice are more anti-inflammatory and polarize towards a M2 phenotype following IL-4 stimulation.</p>

<p>S47 mice are less responsive to PD-L1 blockade therapy. <b>A,</b> Tumor growth curves for P47 and S47 treated with rat IgG2b isotype control antibody or anti-PD-L1 following MC38 cell injections. <i>n</i> = 7 control; 5 9 anti-PD-L1; 10 anti-PD-L1. <b>B,</b> Graph showing the frequency of palpable tumors in receiving antibody. <b>C</b> <b>D,</b> Individual tumor each mouse Statistics were derived from Wilcoxon rank-sum...

<p>S47-derived T cells display a steady-state deficit in effector T-cell function after stimulation. RBC-depleted splenocytes from either S47 or P47 mice were stimulated with PMA/Ionomycin, Concanavalin A, anti-CD3/CD28 Dynabeads, then assayed for cytolytic markers and cytokine production via multiparametric flow cytometry. Values normalized to negative control wells receiving no Data are derived four independent experiments. <b>A–C,</b> Differences...

<p>S47-derived T cells display a steady-state deficit in effector T-cell function after stimulation. RBC-depleted splenocytes from either S47 or P47 mice were stimulated with PMA/Ionomycin, Concanavalin A, anti-CD3/CD28 Dynabeads, then assayed for cytolytic markers and cytokine production via multiparametric flow cytometry. Values normalized to negative control wells receiving no Data are derived four independent experiments. <b>A–C,</b> Differences...

<p>Differences in memory T-cell formation and chemokine receptor usage S47 mice. Splenocytes derived from non–tumor-bearing, male P47 mice between the ages of 6 10 weeks were analyzed by flow cytometry for differences baseline phenotypes. Data are five independent cohorts (<i>n</i> = 27 S47, <i>n</i> 26 P47), all panels incorporate multiple cohorts. <b>A</b> <b>B,</b> Frequencies total (CD44<sup>+</sup>) central...

<p>S47 mice are less responsive to PD-L1 blockade therapy. <b>A,</b> Tumor growth curves for P47 and S47 treated with rat IgG2b isotype control antibody or anti-PD-L1 following MC38 cell injections. <i>n</i> = 7 control; 5 9 anti-PD-L1; 10 anti-PD-L1. <b>B,</b> Graph showing the frequency of palpable tumors in receiving antibody. <b>C</b> <b>D,</b> Individual tumor each mouse Statistics were derived from Wilcoxon rank-sum...

<p>Table S1 and Table S2</p>

<p>Tumor-bearing S47 mice harbor more immunosuppressive splenic immune cell profiles. <b>A,</b> Flow cytometry analyses on splenocytes from TBM for percent positive MDSCs in P47 and mice, respectively. Bar graph right shows the out of total CD45<sup>+</sup> cells. <i>n</i> = 5 per group. <b>B,</b> indicated activation markers macrophages spleen. Histograms top show mean fluorescent intensity (MFI) MHC I histograms bottom MFI CD86. The red...

<p>The tumor growth advantage in S47 mice is abolished following CD8<sup>+</sup> T-cell depletion. <b>A,</b> Illustration of the experimental approach. Replicate P47 and were injected subcutaneously with 1 × 10<sup>6</sup> MC38 cells. At day 19, spleens tumors from harvested analyzed by flow cytometry. <b>B,</b> Tumor curves for <i>n</i> = 5 per group. Linear mixed model used statistical analysis. **, <i>P</i> <...

<p>Tumor-infiltrating T cells in S47 mice display uniquely elevated transcription factor profiles. Tumors and spleens were harvested 21 days after injection of MC38 analyzed for expression by intranuclear flow cytometry. <b>A,</b> The percentage proliferating (Ki67<sup>+</sup>) TILs P47 mice. <b>B,</b> Frequency Eomes<sup>+</sup> or Tbet<sup>+</sup> <b>C,</b> expressing mTOR phosphorylated at serine 2448...

<p>Figure S1 shows BMDMs from S47 mice are more anti-inflammatory and polarize towards a M2 phenotype following IL-4 stimulation.</p>

<p>Tumor-infiltrating T cells in S47 mice display uniquely elevated transcription factor profiles. Tumors and spleens were harvested 21 days after injection of MC38 analyzed for expression by intranuclear flow cytometry. <b>A,</b> The percentage proliferating (Ki67<sup>+</sup>) TILs P47 mice. <b>B,</b> Frequency Eomes<sup>+</sup> or Tbet<sup>+</sup> <b>C,</b> expressing mTOR phosphorylated at serine 2448...

<p>Figure S2 shows that the tumor microenvironment in both P47 and S47 mice is comprised of similar proportions subpopulations immune cells with phenotypes.</p>

<p>Differences in memory T-cell formation and chemokine receptor usage S47 mice. Splenocytes derived from non–tumor-bearing, male P47 mice between the ages of 6 10 weeks were analyzed by flow cytometry for differences baseline phenotypes. Data are five independent cohorts (<i>n</i> = 27 S47, <i>n</i> 26 P47), all panels incorporate multiple cohorts. <b>A</b> <b>B,</b> Frequencies total (CD44<sup>+</sup>) central...