TRB CDR3与HBV表位的化学亲和性相关,与肝细胞癌和无病生存期延长相关。
TRB CDR3 chemical complementarity with HBV epitopes correlates with increased hepatocellular carcinoma, disease-free survival.
发表日期:2023 Aug
作者:
Joanna J Song, Andrea Chobrutskiy, Boris I Chobrutskiy, Konrad J Cios, Taha I Huda, Rachel A Eakins, Michael J Diaz, George Blanck
来源:
JOURNAL OF MEDICAL VIROLOGY
摘要:
相对于膀胱和皮肤等部位,肝脏是免疫特权的场所。为了研究肝癌环境中免疫反应的减弱,我们比较了从肝细胞癌(HCC)和其他六种癌症中获得的适应性免疫受体(IR)重组序列的数量和特征。在这些癌症中,HCC的IR重组序列数量最低,并且是唯一一种具有免疫球蛋白而不是T细胞受体重组序列数量更多的癌症。为了更好地了解肿瘤微环境中获得的适应性IR对HCC病例结果的影响,我们对HCC肿瘤TRB和IGH互补决定区-3(CDR3)氨基酸(AA)序列以及已知的乙型肝炎病毒(HBV)表位之间的化学互补性进行了定量分析。HCC驻留CDR3和三个HBV表位之间的高化学互补性与提高的生存概率相关,这包括了代表不同CDR3恢复算法的两个CDR3来源。这些结果表明CDR3 AA序列有潜力作为HCC患者分层的生物标志物,以及未来治疗方法的指导。© 2023 Wiley Periodicals LLC.
The liver is a site of immune privilege, compared with the bladder and skin, for example. To study this attenuation of the immune response in the cancer setting, we compared quantities and features of adaptive immune receptor (IR) recombination reads obtained from hepatocellular carcinoma (HCC) and six other cancers. Of these cancers, HCC had the lowest numbers of IR recombination reads and was the only cancer with a greater number immunoglobulin rather than T-cell receptor recombination reads. To better understand the role of adaptive IRs obtained from the tumor microenvironment in shaping the outcome of HCC cases, we quantified the chemical complementarity between HCC tumor TRB and IGH complementarity determining region-3 (CDR3) amino acid (AA) sequences, and known hepatitis B virus (HBV) epitopes. High chemical complementarity between HCC-resident CDR3s and three HBV epitopes correlated with increased survival probabilities, for two sources of CDR3s representing different CDR3 recovery algorithms. These results suggest the potential of CDR3 AA sequences as biomarkers for HCC patient stratification and as guides for future development of therapeutics.© 2023 Wiley Periodicals LLC.