杂合子丢失
免疫系统
多发性骨髓瘤
CD8型
癌症研究
医学
等位基因
内科学
肿瘤科
免疫学
生物
遗传学
基因
作者
Yue Wang,Jiadai Xu,Tianwei Lan,Chi Zhou,Peng Liu
摘要
Abstract Objectives Intratumor heterogeneity (ITH) is an important factor for clinical outcomes in patients with multiple myeloma (MM). High ITH has been proven to be a key reason for tumor immune escape and treatment resistance. Neoantigens are thought to be associated with ITH, but the specific correlation and functional basis for this remains unclear. Methods We study this question through the whole‐exome sequencing (WES) data from 43 high ITH newly diagnosed MM patients in our center. Mutant allele tumor heterogeneity (MATH) was conducted to quantify ITH. The cutoff value for high intratumor heterogeneity was determined by comparing MATH of different kinds of tumors. NeoPredPipe was performed to predict neoantigens and binding affinity. Results Compared to other tumors, MM has a relatively low tumor mutation burden but a high ITH. Patients with high MATH had significantly shorter progression‐free survival times than those with low MATH ( p = 0.001). In high ITH samples, there is a decrease in strong‐binding neoantigens ( p = 0.019). The loss of strong‐binding neoantigens is a key factor for insensitivity to therapy ( p = 0.015). Loss of heterozygosity in HLA was not observed. In addition, patients with fewer neoantigens loss had higher rates of disease remission ( p = 0.047). CD8 + T cells ( p = 0.012) and NK cells ( p = 0.011) decreased significantly in patients with high neoantigens loss rate. A prediction model based on neoantigens was built to evaluate the strength of immune escape. Conclusion The loss of strong‐binding neoantigens explains why tumors with high ITH have a higher degree of immune escape and may be feasible for deciding the clinical treatment of MM.
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