Background: This study focuses on the evaluation of intratumoral immune infiltrates of the Qk/trp53/Pten (QPP) triple-knockout mouse model of glioblastoma with the purpose of establishing its relevance compared to the human disease. This included an analysis at the single cell level, of immune cells composition in both spontaneous and implanted mouse tumors and of samples obtained from human tumor resections. Methods: We analyzed a cohort of fifteen spontaneous QPP mice, nine implanted QPP mice and 10 glioma patients by standard immune profiling methods such as IHC. Of those, we analyzed three spontaneous QPP mice, three implanted QPP mice, and 10 glioma patients by single cell RNA sequencing. Results: In the QPP samples we identified a predominantly myeloid cell population of monocytes, macrophages, and microglia, with minor populations of T, B, and NK cells. When comparing spontaneous and implanted mouse samples, we found that there were more neutrophil, T and NKT cells in the implanted model. In human samples, most of the lymphoid and myeloid compartments were immunosuppressive. While the complexity of the myeloid cell populations is preserved between the QPP model and the human disease, we observed significantly more immune-stimulatory populations in the implanted mouse model. Conclusions: We found that, despite differences at the subpopulation level, the immunosuppressive nature of the immune system in glioma, is recapitulated in our mouse model. Although we observed differences in the proportions of immune infiltrates derived from the spontaneous and implanted mouse models and in LGG compared to GBM, the major constituents are present in all cases and these differences may be caused by various etiological or pathogenic influences on tumor-immune interactions. Key Points:• New GBM mouse model for immunotherapy• Single cell profiling of the immune systems in human and mouse GBM
SARS-CoV-2 infections elicit both humoral and cellular immune responses. For the prevention and treatment of COVID19, the disease caused by SARS-CoV-2, it has become increasingly apparent that T cell responses are equally, if not more important than humoral responses in mediating recovery and immune-protection. One of the major challenges in developing T cell-based therapies for infectious and malignant diseases has been the identification of immunogenic epitopes that can elicit a meaningful T cell response. Traditionally, this has been achieved using sophisticated in silico methods to predict putative epitopes deduced from binding affinities and consensus data. Our studies find that, in contrast to current dogma, ‘immunodominant’ SARS-CoV-2 peptides defined by such in silico methods often fail to elicit T cell responses recognizing naturally presented SARS-CoV-2 epitopes.
BACKGROUND The small bowel (SB) is a rare site for distant metastasis. Few recent studies have systematically reported on the clinicopathology and outcomes of SB metastasis. This study aimed to describe the clinicopathology and outcomes of SB metastasis. METHODS A retrospective study involving patients diagnosed with SB metastasis at a single medical center between January 2009 and December 2019 was conducted. Patients with secondary SB cancer with direct invasion or peritoneal carcinomatosis by a primary tumor were excluded. The demographic characteristics of the patients, clinical patterns of primary cancer and SB metastasis, and outcomes were analyzed. RESULTS During the 10-year period, we identified 31 patients eligible for analysis. The female:male ratio was 8:24, and the median patient age was 63.5 years. Metastasis of lung cancer to the SB was noted most frequently. Most patients presented with abdominal pain, gastrointestinal bleeding, or abnormal imaging findings. The interval between primary cancer and SB metastasis was 19.2 months. Sole SB metastasis was noted in 20 patients (64.5%). Twenty-two (70.1%) patients underwent surgical intervention. The median survival was 6.6 months. Conclusions Distant metastasis of other primary cancers to the SB is noted extremely rarely. The presence of SB metastasis indicated extremely poor prognosis. Surgery plays an important role in ameliorating critical symptoms However, surgery does not confer survival benefits.
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