B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer.
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ABSTRACT:
SUBMITTER: Pylaeva E
PROVIDER: S-EPMC8234083 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Loco-regional control (LRC) is a major clinical endpoint after definitive radiochemotherapy (RCT) of head and neck cancer (HNC). Radiomics has been shown a promising biomarker in cancer research, however closer related to primary tumor control than composite endpoints. Radiomics studies often focus on the analysis of primary tumor (PT). We hypothesize that the combination of PT and lymph nodes (LN) radiomics better predicts LRC in HNC treated with RCT. Radiomics analysis was performed in CT images of 128 patients using Z-Rad implementation (training n?=?77, validation n?=?51). 285 features were extracted from PT and involved LN. Features were preselected with the maximum relevance minimum redundancy method and the multivariate Cox model was trained using least absolute shrinkage and selection operator. The mixed model was based on the combination of PT and LN radiomics, whereas the PT model included only the PT features. The mixed model showed significantly higher performance than the PT model (p?<?0.01), c-index of 0.67 and 0.63, respectively; and better risk group stratification. The clinical nodal status was not a significant predictor in the combination with PT radiomics. This study shows that the LRC can be better predicted by expansion of radiomics analysis with LN features.
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Project description:Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.
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Project description:Aim: The purpose of this study was to assess the ability of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of cancerous lymph nodes. Methods: Contrast-enhanced ultrasonography was performed in the cervical nodules of included patients, and the diagnoses were confirmed by pathological examination. Contrast-enhanced ultrasonography images and parameters of head and neck lymphomas were compared with those of cancerous lymph nodes. Besides, receiver operating characteristic curve was operated to access the diagnostic value of CEUS. Results: Finally, a total of 63 head and neck lymphomas and 80 cervical cancerous lymph nodes were enrolled in this study. Results showed that the CEUS images of lymphoma were mainly characterized by homogeneous enhancement (71.43%), and approximately half of them were centripetal perfusion (58.73%), whereas most CEUS images of cancerous lymph nodes were inhomogeneous enhancement (82.50%) and centripetal perfusion (92.50%). Quantitative analysis of CEUS parameters indicated that PI (derived peak intensity) and AUC (area under the curve) of lymphomas were both lower than those of cancerous lymph nodes (PI: 8.78 vs. 10.51, AUC: 652.62 vs. 784.09, respectively) (P < 0.05). Receiver operating characteristic analysis showed that the sensitivity of CEUS parameters in the differential diagnosis was significant (80.00%), although the specificity was not high (47.62%). When parameters were combined with the image features, the accuracy of diagnosis was greatly improved (from 0.655 to 0.899). Conclusion: Contrast-enhanced ultrasonography could be a promising tool for the differential diagnosis of head and neck lymphomas and cancerous lymph nodes.
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Project description:CD169 (sialoadhesin) is a sialic acid receptor that is expressed on specific macrophages such as lymph node sinus macrophages. Animal studies have suggested that CD169(+) macrophages have a pro-inflammatory property, however, the role of these cells in human diseases has not been clarified. In our in vitro experiments with human macrophages, pro-inflammatory cytokines, such as type 1 interferon, induced strong expression of CD169, suggesting that CD169 might be a specific marker of inflammatory macrophages. To examine the role of CD169 in antitumor immunity, we examined the expression of CD169 in regional lymph nodes (RLNs) and its association with overall survival in colorectal carcinoma (CRC). In a clinicopathological analysis on 83 CRC patients, paraffin-embedded specimens were evaluated for CD169 expression of RLN macrophages by immunohistochemistry. We found, for the first time, a high density of CD169(+) macrophages was significantly associated with longer overall survival; multivariate analysis showed that the ratio of CD169(+) cells to CD68(+) cells was an independent prognostic factor. The majority of CD169(+) macrophages were in direct contact with CD8(+) T cells expressing CD43, a major ligand of CD169. We also found that the density of CD169(+) macrophages had a positive correlation with the number of CD8(+) cytotoxic T cells infiltrating tumor tissues. These data suggest that CD169(+) macrophages in RLNs promote CD8(+) T-cell-mediated antitumor immunity and are associated with a better prognosis for CRC patients. CD169(+) macrophages in RLNs could be a useful marker for assessing clinical prognosis and monitoring antitumor immunity in patients with CRC.
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Project description:BackgroundA dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation.ObjectivesTo understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed.Materials and methodsLymph nodes from the cervical, mediastinal, and hilar regions were extracted from autopsies of patients with lethal COVID-19 (n = 20). Histomorphological characteristics, SARS-CoV‑2 qRT-PCR, and gene expression profiling on common genes involved in immunologic response were analyzed.ResultsLymph nodes displayed moderate to severe capillary stasis and edema, an increased presence of extrafollicular plasmablasts, mild to moderate plasmacytosis, a dominant population of CD8+ T‑cells, and CD11c/CD68+ histiocytosis with hemophagocytic activity. Out of 20 cases, 18 presented with hypoplastic or missing germinal centers with a decrease of follicular dendritic cells and follicular T‑helper cells. A positive viral load was detected by qRT-PCR in 14 of 20 cases, yet immunohistochemistry for SARS-CoV-2 N-antigen revealed positivity in sinus histiocytes of only one case. Gene expression analysis revealed an increased expression of STAT1, CD163, granzyme B, CD8A, MZB1, and PAK1, as well as CXCL9.ConclusionsTaken together, our findings imply a dysregulated immune response in lethal COVID-19. The absence/hypoplasia of germinal centers and increased presence of plasmablasts implies a transient B‑cell response, implying an impaired development of long-term immunity against SARS-CoV‑2 in such occasions.
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