Transcriptomic-Assisted Immune and Neoantigen Profiling in Premalignancy

Authors

Kyle Chang
Florencia McAllister
Eduardo Vilar

Publication Date

1-1-2022

Journal

Methods in Molecular Biology

Abstract

Immune-based cancer therapies such as checkpoint inhibitors (CPI) and vaccines have been increasingly studied across different cancer types. Response to such therapies depends on a number of factors such as mutational burden, neoantigen load, presence of tumor infiltrating lymphocytes, among others. Next-generation sequencing (NGS) technologies are particularly attractive to interrogate the immune response compared to traditional assays such as qRT-PCR and immunohistochemistry (IHC) because they enable the discovery of neoantigens and simultaneous profiling of immune infiltration using gene expression on a large scale. Current approaches in immune profiling utilizes whole-exome sequencing (WES) for human leukocyte allele (HLA) typing and neoantigen predictions, and RNA sequencing (RNA-seq) for filtering unexpressed neoantigens and inferring immune infiltration. They have been successfully applied to the tumor setting as there is abundant sample material to perform both experiments. However, premalignant specimens are often much smaller compared to tumors. Therefore, there is a need to explore the viability of adopting a single approach for immune, neoantigen, and mutation profiling. Here, we describe our workflow of using RNA-seq to analyze mutational burden, neoantigen load, and immune expression profile.

Keywords

Antigens, Neoplasm, Humans, Lymphocytes, Tumor-Infiltrating, Mutation, Precancerous Conditions, Transcriptome, Exome Sequencing

DOI

10.1007/978-1-0716-2014-4_7

PMID

34993941

PMCID

PMC11073470

PubMedCentral® Posted Date

5-6-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes