A5081795863- Immunotherapy and Immune Responses
- Immune cells in cancer
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- Gut microbiota and health
- Chemokine receptors and signaling
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Receptor Mechanisms and Signaling
- Cytokine Signaling Pathways and Interactions
- Probiotics and Fermented Foods
- Mast cells and histamine
- Immune Response and Inflammation
- Pediatric health and respiratory diseases
- Inflammatory mediators and NSAID effects
University of Cambridge
2022-2025
The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing microbes with poorer prognosis; however, LPS from diverse bacterial species can range immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes 112 patients melanoma, we found that a subset of LPS-producing bacteria encoding...
Regulatory T (T
<p>Supplementary Figure 2: T cell populations in the spleen and tumor of FS120m treated mice. (A) Percentages indicated tumors mice with or control antibodies. (B) spleens (C) Absolute counts exTreg cells Foxp3+ RFP+ Treg per gram (left) whole (right) animals. (D) IFN-γ producing FS120m-treated (E) TNF * P ≤ 0.05, ** 0.01. Student’s t test. Bars error are mean s.e.m.</p>
<p>Supplementary Figure 3: Increased IL-2 expression by conventional CD4+ and CD8+ T cells with FS120m treatment. Representative plots (left) replicate measurements (right) of IL-2+ Tconv in the spleen draining lymph nodes on day 18 post tumor implantation. *** P ≤ 0.001, **** 0.0001. Unpaired Student’s t test. Bars error are mean s.e.m.</p>
<p>Supplementary Figure 1: OX40 and CD137 are highly expressed on Treg cells. Representative plots showing OX40+ (left) CD137+ (right) SP resting or activated cells from the spleen tumor day 18 post implantation. ** P ≤ 0.01, *** 0.001, **** 0.0001. One-way ANOVA with Tukey’s correction for multiple comparisons. Bars error mean s.e.m.</p>
Natural killer (NK) cells are critical to immune surveillance against infections and cancer. Their role in requires that NK present within tissues a quiescent state. Mechanisms by which remain incompletely elucidated. The transcriptional repressor BACH2 plays the adaptive system, but its function innate lymphocytes has been unclear. Here, we show acts as an intrinsic negative regulator of cell maturation function. is expressed developing mature promotes maintenance immature restricting their...
Abstract Immune checkpoint inhibitors (ICI), such as anti-PD-1, have revolutionized cancer treatment, but they are only effective for a minority of patients. The gut microbiome plays crucial role in modulating immunotherapy treatment responses, and previous studies correlated lipopolysaccharide (LPS)-producing microbes with poorer prognosis. However, LPS from diverse bacterial species activities ranging immunostimulatory to inhibitory. By functionally analyzing fecal metagenomes 112 melanoma...
<div>Abstract<p>Regulatory T cells (Treg) are highly enriched within many tumors and suppress immune responses to cancer. There is intense interest in reprogramming Tregs contribute antitumor immunity. OX40 CD137 expressed on Tregs, activated memory cells, NK cells. In this study, using a novel bispecific antibody targeting mouse (FS120m), we show that OX40/CD137 agonism induces potent immunity partially dependent upon IFNγ production by functionally reprogrammed Tregs. Treatment...
Regulatory T cells (Treg) are highly enriched within many tumors and suppress immune responses to cancer. There is intense interest in reprogramming Tregs contribute antitumor immunity. OX40 CD137 expressed on Tregs, activated memory cells, NK cells. In this study, using a novel bispecific antibody targeting mouse (FS120m), we show that OX40/CD137 agonism induces potent immunity partially dependent upon IFNγ production by functionally reprogrammed Tregs. Treatment of tumor-bearing animals...
<p>Supplementary Figure 2: T cell populations in the spleen and tumor of FS120m treated mice. (A) Percentages indicated tumors mice with or control antibodies. (B) spleens (C) Absolute counts exTreg cells Foxp3+ RFP+ Treg per gram (left) whole (right) animals. (D) IFN-γ producing FS120m-treated (E) TNF * P ≤ 0.05, ** 0.01. Student’s t test. Bars error are mean s.e.m.</p>
<p>Supplementary Figure 3: Increased IL-2 expression by conventional CD4+ and CD8+ T cells with FS120m treatment. Representative plots (left) replicate measurements (right) of IL-2+ Tconv in the spleen draining lymph nodes on day 18 post tumor implantation. *** P ≤ 0.001, **** 0.0001. Unpaired Student’s t test. Bars error are mean s.e.m.</p>
<p>Supplementary Figure 1: OX40 and CD137 are highly expressed on Treg cells. Representative plots showing OX40+ (left) CD137+ (right) SP resting or activated cells from the spleen tumor day 18 post implantation. ** P ≤ 0.01, *** 0.001, **** 0.0001. One-way ANOVA with Tukey’s correction for multiple comparisons. Bars error mean s.e.m.</p>
<p>Supplementary Figure 3: Increased IL-2 expression by conventional CD4+ and CD8+ T cells with FS120m treatment. Representative plots (left) replicate measurements (right) of IL-2+ Tconv in the spleen draining lymph nodes on day 18 post tumor implantation. *** P ≤ 0.001, **** 0.0001. Unpaired Student’s t test. Bars error are mean s.e.m.</p>
<p>Supplementary Figure 1: OX40 and CD137 are highly expressed on Treg cells. Representative plots showing OX40+ (left) CD137+ (right) SP resting or activated cells from the spleen tumor day 18 post implantation. ** P ≤ 0.01, *** 0.001, **** 0.0001. One-way ANOVA with Tukey’s correction for multiple comparisons. Bars error mean s.e.m.</p>
<p>Supplementary Figure 2: T cell populations in the spleen and tumor of FS120m treated mice. (A) Percentages indicated tumors mice with or control antibodies. (B) spleens (C) Absolute counts exTreg cells Foxp3+ RFP+ Treg per gram (left) whole (right) animals. (D) IFN-γ producing FS120m-treated (E) TNF * P ≤ 0.05, ** 0.01. Student’s t test. Bars error are mean s.e.m.</p>
<p>Supplementary Figure 3: Increased IL-2 expression by conventional CD4+ and CD8+ T cells with FS120m treatment. Representative plots (left) replicate measurements (right) of IL-2+ Tconv in the spleen draining lymph nodes on day 18 post tumor implantation. *** P ≤ 0.001, **** 0.0001. Unpaired Student’s t test. Bars error are mean s.e.m.</p>
<p>The antitumor efficacy of OX40/CD137 dual agonism is partially dependent upon IFNγ production by Tregs and/or their lineage-instable progeny. <b>A,</b> PCR genotyping CD8<sup>+</sup>, CD4<sup>+</sup> Foxp3-GFP<sup>−</sup> Tconv, and Foxp3-GFP<sup>+</sup> sorted from the spleens mice with indicated genotypes after treatment tamoxifen. have cell-specific excision only in possessing both...
<p>OX40/CD137 bispecific agonist (FS120m) drives functional fragility and lineage instability of Tregs. <b>A,</b> Schema (top) showing tamoxifen FS120m treatment schedule. Tumor measurements (bottom) at indicated timepoints after MC38 tumor implantation. (Solid line, mean values; dotted lines, individual mouse curves.) <b>B,</b> Representative plots percentages CD4<sup>+</sup> GFP<sup>+</sup> RFP<sup>+</sup> Tregs...
<p>Treg instability is induced by OX40/CD137 bispecific agonist (FS120m) and not anti-PD1 treatment. <b>A,</b> Representative plots showing the frequency of IFNγ<sup>+</sup> cells CD4<sup>+</sup> Foxp3<sup>−</sup> Tconv Foxp3<sup>+</sup> Tregs in blood on day 18 after MC38 tumor implantation. <b>B,</b> Quantification statistical analysis data shown <b>A</b>. Data were analyzed ordinary one-way ANOVA...
<p>OX40/CD137 dual agonism results in decreased CD25 expression and IL2 responsiveness of Tregs. <b>A,</b> Representative histograms replicate measurements showing on CD4<sup>+</sup> Tregs from the spleen (left) tumor-draining lymph node (right). <b>B,</b> Schema setup <i>ex vivo</i> assay (left), Foxp3-GFP (center), Treg count (right) after 4 days culture with indicated concentrations IL2. <b>C,</b> representing treatment...
<p>OX40 and CD137 are highly coexpressed on tumor-associated Tregs. <b>A,</b> Representative plots showing expression of OX40 resting activated CD4<sup>+</sup> Tregs, Tconv cells, CD8<sup>+</sup> T cells from the spleens tumors mice inoculated with MC38 cells. <b>B</b> <b>C,</b> Quantification CD44<sup>−</sup> CD62L<sup>+</sup> (left) CD44<sup>+</sup> CD62L<sup>−</sup> (right)...
<p>Treg instability is induced by OX40/CD137 bispecific agonist (FS120m) and not anti-PD1 treatment. <b>A,</b> Representative plots showing the frequency of IFNγ<sup>+</sup> cells CD4<sup>+</sup> Foxp3<sup>−</sup> Tconv Foxp3<sup>+</sup> Tregs in blood on day 18 after MC38 tumor implantation. <b>B,</b> Quantification statistical analysis data shown <b>A</b>. Data were analyzed ordinary one-way ANOVA...
<div>Abstract<p>Regulatory T cells (Treg) are highly enriched within many tumors and suppress immune responses to cancer. There is intense interest in reprogramming Tregs contribute antitumor immunity. OX40 CD137 expressed on Tregs, activated memory cells, NK cells. In this study, using a novel bispecific antibody targeting mouse (FS120m), we show that OX40/CD137 agonism induces potent immunity partially dependent upon IFNγ production by functionally reprogrammed Tregs. Treatment...
<p>Supplementary Figure 2: T cell populations in the spleen and tumor of FS120m treated mice. (A) Percentages indicated tumors mice with or control antibodies. (B) spleens (C) Absolute counts exTreg cells Foxp3+ RFP+ Treg per gram (left) whole (right) animals. (D) IFN-γ producing FS120m-treated (E) TNF * P ≤ 0.05, ** 0.01. Student’s t test. Bars error are mean s.e.m.</p>