Predictive Panel for Immunotherapy in Lower-Grade Glioma.

BACKGROUND: The main treatment of lower-grade glioma (LGG) is still surgical resection followed by radiotherapy and/or chemotherapy, which has certain limitations, including side effects and drug resistance. Immunotherapy is a promising treatment for LGG, but it is generally hindered by the tumor microenvironment with the limited expression of tumor antigens.

METHODS: We integrated RNA sequencing data sets and clinical information and conducted consistent cluster analysis to explore the most suitable patients for immune checkpoint therapy. Gene set enrichment analysis, UMAP analysis, mutation correlation analysis, TIMER analysis and TIDE analysis were used to identify the immune characteristics of three immune subtypes and the feasibility of five antigens as immune checkpoint markers.

RESULTS: We analyzed the isolation and mutation of homologous recombination repair genes（HRR） of the three immune subtypes, and the HRR genes of the three subtypes were obviously segregated. Among them, IS2 subtype has a large number of HRR gene mutations, which increases the immunogenicity of tumors, which is consistent with the results of tumor mutation load analysis of three immune subtypes. Then we evaluated the immune cell infiltration of immune subtypes and found that IS2 and IS3 subtypes were rich in immune cells. It is worth noting that there are many Treg cells and NK cells in IS1 subtype. In addition, when analyzing the immune checkpoint gene expression of the three subtypes, we found that they were up-regulated most in IS2 subtypes compared with other subtypes. Then when we further confirmed the role of immune-related genes in LGG, through TIDE analysis and TISIDB analysis, we obtained five markers that can predict the efficacy of ICB in patients with LGG. In addition, we confirmed that they were associated with poor prognosis through survival analysis.

CONCLUSIONS: We obtained three reliable immune subtypes, and patients with the IS2 subtype are suitable for immunotherapy, in which NAMPT, SLC11A1, TNC, VIM, and SPP1 are predictive panel markers for ICB in the LGG group. Our findings provide a rationale for immunotherapy selection and prediction of patient prognosis in LGG patients.