Complete small bowel obstruction caused by metastasis from primary nasopharyngeal carcinoma

We here report the first case in the literature on a surgical emergency of complete small bowel obstruction caused by metastasis from nasopharyngeal carcinoma nine months after the primary tumor was treated with concurrent chemoradiation. The patient achieved prolonged survival with prompt surgical treatment followed by systemic chemotherapy

Human Leukocyte Antigen (HLA) A*1101-restricted Epstein-Barr virus-specific T-cell receptor gene transfer to target Nasopharyngeal carcinoma

Infusing virus-specific T-cells is effective treatment for rare Epstein-Barr virus (EBV)-associated post-transplant lymphomas and more limited success has been reported using this approach to treat a far more common EBV-associated malignancy, Nasopharyngeal carcinoma (NPC). However, current approaches using EBV-transformed lymphoblastoid cell lines to reactivate EBV-specific T-cells for infusion take 2-3 months of in vitro culture and favour outgrowth of T-cells targeting viral antigens expressed within EBV+ lymphomas but not NPC. Here we explore T-cell receptor (TCR) gene transfer to rapidly and reliably generate T-cells specific for the NPC-associated viral protein LMP2. We cloned a HLA A*1101-restricted TCR, which would be widely applicable since 40% of NPC patients carry this HLA allele. Studying both wild-type and modified forms we have optimised expression of the TCR and demonstrated high avidity antigen-specific function (proliferation, cytotoxicity, cytokine release) in both CD8+ and CD4+ T-cells. The engineered T-cells also inhibited LMP2+ epithelial tumour growth in a mouse model. Furthermore, transduced T-cells from patients with advanced NPC lysed LMP2-expressing NPC cell lines. Therefore, using this approach, within a few days large numbers of high avidity LMP2-specific T-cells can be reliably generated to treat NPC, providing an ideal clinical setting to test TCR gene transfer without the risk of autoimmunity through targeting self-antigens

The photometric observation of the quasi-simultaneous mutual eclipse and occultation between Europa and Ganymede on 22 August 2021

Mutual events (MEs) are eclipses and occultations among planetary natural satellites. Most of the time, eclipses and occultations occur separately. However, the same satellite pair will exhibit an eclipse and an occultation quasi-simultaneously under particular orbital configurations. This kind of rare event is termed as a quasi-simultaneous mutual event (QSME). During the 2021 campaign of mutual events of jovian satellites, we observed a QSME between Europa and Ganymede. The present study aims to describe and study the event in detail. We observed the QSME with a CCD camera attached to a 300-mm telescope at the Hong Kong Space Museum Sai Kung iObservatory. We obtained the combined flux of Europa and Ganymede from aperture photometry. A geometric model was developed to explain the light curve observed. Our results are compared with theoretical predictions (O-C). We found that our simple geometric model can explain the QSME fairly accurately, and the QSME light curve is a superposition of the light curves of an eclipse and an occultation. Notably, the observed flux drops are within 2.6% of the theoretical predictions. The size of the event central time O-Cs ranges from -14.4 to 43.2 s. Both O-Cs of flux drop and timing are comparable to other studies adopting more complicated models. Given the event rarity, model simplicity and accuracy, we encourage more observations and analysis on QSMEs to improve Solar System ephemerides.Comment: 23 pages, 5 appendixes, 16 figures, 7 table

T cell homing to nasopharyngeal carcinoma

Undifferentiated nasopharyngeal carcinoma (NPC) is a very good candidate disease for treatment with adoptive T cell transfer. Uniformly Epstein-Barr virus (EBV)+, these tumours reportedly have functional antigen processing and presentation machinery and express viral proteins that contain known cytolytic T cell target epitopes. This raises the possibility that boosting relevant EBV-specific T cell immunity in NPC patients might defeat the tumour. The persistent nature of EBV infection may also encourage the long-term survival of therapeutically administered virus-specific cells. However, efficient delivery of tumour-specific T cells from the circulation to solid tumour tissue is a clear requirement for effective cellular therapy, yet the mechanisms by which T cells gain entry to NPC tumours have not yet been determined. The malignant cells of NPC are usually associated with a substantial lymphoid infiltrate mainly consisting of T cells. Using unmanipulated diagnostic biopsy samples, we have characterised chemokine receptor expression (CR) on tumour-infiltrating T cells, and established whether specific chemokine ligands are detectable at the NPC tumour site. We found that functional CXCR6 and CCR5 were expressed on tumour infiltrating T cells, consistent with the presence of specific ligands for these receptors at the tumour site. Furthermore, our data suggests that effector and regulatory cells may use shared homing mechanisms to gain entry to NPC tumours

CXCR6 and CCR5 localize T lymphocyte subsets in nasopharyngeal carcinoma

The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T cell recruitment to this tumor are poorly understood. Comparing memory T cell subsets that have naturally infiltrated NPC tissue with their counterparts from matched blood revealed enrichment of CD8�, CD4�, and regulatory T cells expressing the chemokine receptor CXCR6 in tumor tissue. CD8� and (nonregulatory) CD4� T cells also were more frequently CCR5� in tumor than in blood. Ex vivo studies demonstrated that both receptors were functional. CXCL16 and CCL4, unique chemokine ligands for CXCR6 and CCR5, respectively, were expressed by the malignant cells in tumor tissue from the majority of NPC cases, as was another CCR5 ligand, CCL5. The strongest expression of CXCL16 was found on tumor-infiltrating cells. CCL4 was detected on the tumor vasculature in a majority of cases. These findings suggest that CXCR6 and CCR5 play important roles in T cell recruitment and/or retention in NPC and have implications for the pathogenesis and treatment of this tumo