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关键词： genomic full-length   HLA-DRB1*13:97:01   PacBio sequencing  

摘要： The complete genomic sequence of HLA-DRB1*13:97:01 was determined using a PacBio sequencing approach conducted in China.

关键词： Tumor-infiltrating lymphocytes   Cancer Immunotherapy   Combinatory therapy  

摘要： Background & AimTumor-infiltrating lymphocyte (TIL) therapy has shown limited efficacy in cold tumors due to impaired infiltration, suppressive microenvironment, and defective tumor antigen presentation. Recent advancements in expansion protocols and combination therapies offer promising strategies to address these challenges. MethodologyTILs from renal cell carcinoma (RCC), glioblastoma (GBM), prostate cancer (PRC) and pancreatic cancer (PCA) were expanded with IL-2/IL-15/IL-21 in a closed perfusion bioreactor. TIL pharmacokinetics (PK) and tumor infiltration were analyzed using T-cell receptor (TCR) next-generation sequencing, while pharmacodynamics (PD) were assessed by FACS, RNA-seq and ELISA. ResultsExpanded TIL products exhibited high CD8/CD4 ratios, robust cytokine production, degranulation and autologous tumor-specific killing. Patients received a single cyclophosphamide dose one day before infusion, followed by IL-2 administrations. GBM patient demonstrated complete tumor regression 22 days after the second infusion, followed by increased IFN-γ levels and memory T-cell frequency in the blood. High tumor infiltration of TIL-derived clonotypes, enhanced immunological synapse and T-cell activation RNA signatures were observed in tumor samples after the infusions. CD4+ TILs displayed high TCR diversity but limited infiltration, while CD8+ TILs showed robust tumor infiltration and expansion in vivo. RCC patient evolved from stable disease (SD) after two infusions to partial response (PR) post-third infusion, with sustained good clinical condition. PCA and PRC patients transitioned from SD post-first infusion to PR after the second dose. Notably, PRC achieved a complete response exceeding five years, with undetectable PSA levels when the third infusion was combined with anti-PD-1. This combination expanded previously infused TIL-derived clonotypes in blood and tumor, resulting in sustained persistence and infiltration. Across all cases, high TIL infiltration corr

关键词： gene deletion   haplotypes   histocompatibility testing   HLA-B gene  

摘要： Targeted next generation sequencing-based HLA typing of a 17-year-old female transplant patient showed homozygosity for the HLA-B allele. The segregation analysis of HLA haplotypes of family members only allowed the conclusion that the B-allele was deleted in the haplotype inherited from the father and accordingly paternal grandfather, resulting in false homozygous genotyping. The subsequent whole-genome sequencing of the patient and her father confirmed an approximately 85 kb deletion at 6p21.33 from the 5 ' end of the HLA-B to the 3 ' end of the HLA-C gene extending telomeric to HLA-C.

关键词： haploidentical stem cell transplantation donors and patients   HLA   KIR   KIR genotype   transplantation  

摘要： There is limited information regarding the influence of KIR genotype, compared to the HLA system, in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). This study aimed to determine the frequencies of KIR genotypes in Spanish haematologic patients undergoing haplo-HSCT. A study was conducted on 113 oncohaematological patients and their donors, treated across five centres that are members of the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC). KIR typing was performed using PCR-rSSO or PCR-SSP. KIR genotypes were identified using the KIR Allele Frequency Net Database. Among donors, the most frequent KIR genotypes were Type 1 (28.3%), Type 2 (12.4%) and Type 4 (10.6%). In patients, Genotypes 1 (23.9%), 4 (23%) and 2 (14.2%) were most prevalent. Donors exhibited AA centromeric (46%) and telomeric (59.3%) types, while patients had a higher AB centromeric frequency (52.2%). Differences were observed in the BB centromeric type (3.5% patients;16.8% donors, p = 0.002). The AB KIR genotype was the most common (70.8% donors;75.2% patients). Most were classified as 'neutral' (61.9% donors;73.5% patients). B-content score1 was the most common (48.7% patients;33.6% donors). Notably, classification as best was rare (2.7% patients;16.8% donors, p = 0.002). The study highlights the distribution of KIR genotypes in haplo-HSCT patients and donors, with Genotypes 1, 2 and 4 being the most prevalent. AB KIR genotypes and B-content score 1 were dominant. Moreover, KIR genotypes ID may serve as criteria for future investigation about the immunogenetic predisposition to malignant haematological diseases.

关键词： oral lichen planus   IFN-gamma   IL-4   cytokines   Th1/Th2 balance  

摘要： Introduction: Oral lichen planus (OLP) is a chronic inflammatory disease with immune system dysregulation playing a key role in its pathogenesis. Cytokines such as IFN-gamma and IL-4 are critical in modulating the Th1/Th2 balance, which is implicated in the disease's progression. This study aimed to evaluate the expression of IFN-gamma and IL-4 in the peripheral blood of OLP patients and explore differences between erosive and non-erosive subtypes. Materials and Methods: A retrospective analysis included 58 OLP patients (30 non-erosive and 28 erosive) and 58 healthy controls enrolled from June 2020 to June 2022. mRNA levels of IFN-gamma and IL-4 were quantified using RT-PCR, while protein expression was determined via ELISA. Results: OLP patients demonstrated significantly elevated IFN-gamma and IL-4 mRNA and protein levels compared to healthy controls (p < .05). Both erosive and non-erosive subtypes showed increased cytokine expression (p < .05). IL-4 levels were higher in the erosive subtype (p < .05), while IFN-gamma levels showed no significant difference between subtypes (p > .05). The IFN-gamma/IL-4 ratio was significantly higher in OLP patients than in controls (p < .05), but lower in the erosive subtype compared to the non-erosive group (p < .05). Conclusion: Elevated IFN-gamma and IL-4 expression, particularly the skewed IFN-gamma/IL-4 ratio in erosive OLP, highlights the importance of Th1/Th2 imbalance in OLP pathogenesis. This warrants further investigation into cytokine-targeted therapies for this chronic condition.

关键词： bone marrow transplantation   C*01:285Q   HLA-C   NGS  

摘要： HLA-C*01:285Q differs from HLA-C*01:02:01:01 by a single nucleotide substitution in the start codon.