Anti-Vα24Jα18 TCR Antibody Tunes iNKT Cell Responses to Target and Kill CD1d-negative Tumors in an FcγRII (CD32)-dependent Manner.

Invariant natural killer T (iNKT) cells play an essential role in antitumor immunity by exerting cytotoxicity and producing massive amounts of cytokines. iNKT cells express invariant T-cell receptors (TCR) to recognize their cognate glycolipid antigens such as α-galactosylceramide (α-GalCer) presented on CD1d. We recently reported that iNKT cells recognize CD1d-negative leukemia cell line K562 in a TCR-dependent manner. However, it remains controversial how iNKT cells use TCRs to recognize and exhibit cytotoxic activity toward CD1d-negative tumors cells without CD1d restriction. Here, we report that iNKT cells exerted cytotoxicity toward K562 cells via a carried over anti-Vα24 TCR mAb from positive selection by magnetic bead sorting. We found that addition of the anti-Vα24Jα18 TCR mAb (6B11 mAb) rendered iNKT cells cytotoxic to K562 cells in an FcγRII (CD32)-dependent manner. Moreover, iNKT cells treated with 6B11 mAb became cytotoxic to other CD32+ cell lines (U937 and Daudi). In addition, iNKT cells treated with 6B11 mAb suppressed K562 cell growth in a murine xenograft model in vivo. These data suggest that anti-iNKT TCR mAb treatment of iNKT cells can be applied as a therapeutic strategy to treat CD32+ cancers such as leukemia, lymphoma, and lung cancer. SIGNIFICANCE: Our findings unveiled that iNKT cells recognize and kill CD1d-negative target tumors via the anti-iNKT TCR mAb bound to CD32 at the tumor site, thereby bridging iNKT cells and CD1d-negative tumors. These findings shed light on the therapeutic potential of anti-iNKT TCR mAbs in NKT cell-based immunotherapy to treat CD1d-negative CD32+ cancers.

Impaired Aortic Growth in Neuroblastoma Patients After Intensive Treatment.

PURPOSE: This study evaluated the abdominal aortic diameter in high-risk neuroblastoma (NB) patients and the risk of aortic narrowing following intensive treatment. METHODS: We measured the aortic diameter at four specific levels of the abdominal aorta (diaphragmatic crus, celiac axis, and the root of the superior (SMA) and inferior (IMA) mesenteric arteries) on contrast CT scans. The control group consisted of 56 children with non-oncologic disorders, while the NB group included 35 patients with high-risk abdominal NB. We used regression analysis of age and aortic diameter to determine the regression formula for each level in each group and performed intergroup comparisons using t-test. RESULTS: We evaluated a total of 160 contrast-enhanced CTs performed in the 35 eligible cases. The aortic diameter of pretreated NB patients was not significantly different from the controls. After receiving any treatment, the aortic diameter was significantly smaller in the NB group (p < 0.01 each). Patients who underwent radical surgery, particularly gross total resection (n = 26), had smaller aortic diameters at all levels compared to controls (p < 0.01 each). Patients treated with radiotherapy (RT) had smaller aortic diameters than controls. External beam radiotherapy (EBRT) patients (n = 24) had smaller aortic diameters at all levels except the celiac axis (crus, SMA, IMA; p < 0.01 each), and intraoperative radiotherapy (IORT) ± EBRT patients (n = 5) had smaller aortic diameters at all levels (p < 0.01 each). CONCLUSION: Patients with NB may experience impaired development of the abdominal aorta after multimodal therapy, particularly after RT. Close observation and long-term follow-up is essential to monitor for catastrophic vascular complications. LEVEL OF EVIDENCE: LEVEL III.

Larger Physique as a Risk Factor for Infantile Appendicitis: A Retrospective Study.

The clinical features and risk factors of acute appendicitis in infants are unclear. Our aim was to evaluate the association between anthropometrics and the occurrence of infantile appendicitis. This was a retrospective study of infants (<6 years of age) and school-age children (6-10 years of age) of Asian ethnicity who required hospitalization for appendicitis at our two participating institutions between 2004 and 2018. The Z-score for height, body weight, and body mass index (BMI) was compared between the two groups, as well as between patients presenting with perforated and non-perforated appendicitis. The analysis included data from 73 infants and 362 school-age children. Z-scores were greater in infants than in school-age children for height (0.37 versus -0.03, p = 0.003) and body weight (0.12 versus -0.36, p = 0.023), with no between-group difference for the Z-score of BMI. There was no difference in Z-scores for height, weight, and BMI between the perforated and non-perforated appendicitis infant groups. Infants presenting with acute appendicitis were characterized by a larger physique but with normal proportion. This trend was not observed in school-age children. Therefore, larger infants presenting with abdominal pain should be screened for appendicitis.