Search

Growth of solid tumors is often associated with the development of an immunosuppressive tumor microenvironment (TME). It has been suggested that the influence of the TME may extend beyond the local tumor and results in systemic immunosuppression. Here, we utilize two murine cancer models to explore the influence of solid tumors on the occurrence of alloreactivity-driven GvHD and graft-versus-solid tumor (GvT) effects following MHC-mismatched allogeneic bone marrow transplantation (allo-BMT). Melanoma- or colon carcinoma–bearing C57BL/6 mice did not develop GvHD after BMT even when the bone marrow inoculum was supplemented with donor-type splenocytes. This protection against GvHD required the presence of tumors because its resection prior to allo-BMT promptly resulted in development of GvHD. In addition, tumor-bearing mice given T-cell–depleted allo-BMT (allo-TCD-BMT) failed to develop GvHD and also showed significantly stronger GvT effects than mice given allo-BMT. The GvT effects in allo-TCD-BMT recipients were associated with profound changes in tumor-infiltrating cells compared with that in allo-BMT recipients, with significantly reduced donor-derived regulatory T cells (Treg), increased cytotoxic effector (IFNγhi) CD8 T cells, and increased M1 macrophages (iNOShi, arginaselo, and IL10lo); the use of macrophage-depleted bone marrow abrogated the GvT effects. Collectively, these results indicate that the presence of M1 macrophages may disrupt the generation of donor-type Treg cells so that the immunomodulatory effect of the TME can affect systemic immunity.Significance:These findings show that cells such as T cells or macrophages in the bone marrow inoculum may interfere with the systemic and local immune reactivity against tumors.

Figure S1. Treg cells accumulate at multiple organs in tumor-bearing mice. Figure S2. allo-BMT leads to aGVHD. Figure S3. Treg cells accumulate at multiple organs post-BMT. Figure S4. Efficiency of Treg depletion. Figure S5. Efficiency of thymectomy of B6 mice. Figure S6. T cell add-back abrogates the GVT effect of the TCD transplant. Figure S7. Macrophage loss abrogates the impact of TCD on GVT. Figure S8. M1 polarization disrupts Treg cells expansion.

Supplementary Figure Legend from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination

Supplementary Figure 1 from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination

The translocation t(11;18)(q21;q21) that generates an API2-MALT1 fusion protein is the most common structural abnormality among the genetic defects reported in mucosa-associated lymphoid tissue (MALT)-type lymphomas, and its presence correlates with the apparent lack of further genetic instability or chromosomal imbalances. Hence, constitutive nuclear factor-κB (NF-κB) activation induced by the API2-MALT1 fusion protein is considered essential for B-cell transformation. To examine its role in B-cell development and lymphomagenesis, Eμ-API2-MALT1 transgenic mice were produced. Our data show that expression of the API2-MALT1 fusion protein alone is not sufficient for the development of lymphoma masses within 50 weeks. Nevertheless, API2-MALT1 expression affected B-cell maturation in the bone marrow and triggered the specific expansion of splenic marginal zone B cells. Polyubiquitination of IκB kinase γ (IKKγ), indicative for enhanced NF-κB activation, was increased in splenic lymphocytes and promoted the survival of B cells ex vivo. In addition, we show that the API2-MALT1 fusion resided in the cholesterol- and sphingolipid-enriched membrane microdomains, termed lipid rafts. We provide evidence that association of the MALT1 COOH terminal with the lipid rafts, which is mediated by the API2 portion, is sufficient to trigger NF-κB activation via enhanced polyubiquitination of IKKγ. Taken together, these data support the hypothesis that the API2-MALT1 fusion protein can contribute to MALT lymphoma formation via increased NF-κB activation. (Cancer Res 2006; 66(10): 5270-7)

Although paper-based transmission of medical information might seem outdated, it has proven efficient, and remains structurally safe from massive data leaks. As part of the ICIPEMIR project for improving medical imaging report, we explored the idea of structured data storage within a medical report, by embedding the data themselves in a QR-Code (and no URL-to-the-data). Three different datasets from ICIPEMIR were serialized, then encoded in a QR-Code. We compared 4 compression algorithms to reduce file size before QR-Encoding. YAML was the most concise format (character sparing), and allowed for embedding of a 2633-character serialized file within a QR-Code. The best compression rate was obtained with gzip, with a compression ratio of 2.32 in 15.7ms. Data were easily extracted and decompressed from a digital QR-Code using a simple command line. YAML file was also successfully recovered from the printed QR-Code with both Android and iOS smartphone. Minimal detected size was 3*3cm.

Although paper-based transmission of medical information might seem outdated, it has proven efficient, and remains structurally safe from massive data leaks. As part of the ICIPEMIR project for improving medical imaging report, we explored the idea of structured data storage within a medical report, by embedding the data themselves in a QR-Code (and no URL-to-the-data). Three different datasets from ICIPEMIR were serialized, then encoded in a QR-Code. We compared 4 compression algorithms to reduce file size before QR-Encoding. YAML was the most concise format (character sparing), and allowed for embedding of a 2633-character serialized file within a QR-Code. The best compression rate was obtained with gzip, with a compression ratio of 2.32 in 15.7ms. Data were easily extracted and decompressed from a digital QR-Code using a simple command line. YAML file was also successfully recovered from the printed QR-Code with both Android and iOS smartphone. Minimal detected size was 3*3cm.

To assist public health responses to COVID-19, wastewater-based epidemiology (WBE) is being utilised internationally to monitor SARS-CoV-2 infections at the community level. However, questions remain regarding the sensitivity of WBE and its use in low prevalence settings. In this study, we estimated the total number of COVID-19 cases required for detection of SARS-CoV-2 RNA in wastewater. To do this, we leveraged a unique situation where, over a 4-month period, all symptomatic and asymptomatic cases, in a population of approximately 120,000, were precisely known and mainly located in a single managed isolation and quarantine facility (MIQF) building. From 9 July to 6 November 2020, 24-hr composite wastewater samples (n = 113) were collected daily from the sewer outside the MIQF, and from the municipal wastewater treatment plant (WWTP) located 5 km downstream. New daily COVID-19 cases at the MIQF ranged from 0 to 17, and for most of the study period there were no cases outside the MIQF identified. SARS-CoV-2 RNA was detected in 54.0% (61/113) at the WWTP, compared to 95.6% (108/113) at the MIQF. We used logistic regression to estimate the shedding of SARS-CoV-2 RNA into wastewater based on four infectious shedding models. With a total of 5 and 10 COVID-19 infectious cases per 100,000 population (0.005 % and 0.01% prevalence) the predicated probability of SARS-CoV-2 RNA detection at the WWTP was estimated to be 28 and 41%, respectively. When a proportional shedding model was used, this increased to 58% and 87% for 5 and 10 cases, respectively. In other words, when 10 individuals were actively shedding SARS-CoV-2 RNA in a catchment of 100,000 individuals, there was a high likelihood of detecting viral RNA in wastewater. SARS-CoV-2 RNA detections at the WWTP were associated with increasing COVID-19 cases. Our results show that WBE provides a reliable and sensitive platform for detecting infections at the community scale, even when case prevalence is low, and can be of use as an early warning system for community outbreaks., Graphical abstract Image, graphical abstract