Mutational landscape of immune surveillance genes in diffuse large B-cell lymphoma

ABSTRACT

Introduction

Immune surveillance is the dynamic process whereby the immune system identifies and kills tumor cells based on their aberrant expression of stress-related surface molecules or presentation of tumor neoantigens. It plays a crucial role in controlling the initiation and progression of hematologic cancers such as leukemia and lymphoma, and it has been reported that diffuse large B-cell lymphoma (DLBCL) fails to express specific cell-surface molecules that are necessary for the recognition and elimination of tumor cells.

Areas covered

This review is based on a systematic search strategy to identify relevant literature in the PubMed and Embase databases. Ten candidate genes are identified based on mutational frequency, and functions with detailed mapping performed for hotspot alterations that may have a functional impact on malignant transformation and decreased immune surveillance efficacy.

Expert opinion

Ongoing development of technology and bioinformatics tools combined with data from large clinical cohorts have the potential to define the mutational landscape associated with immune surveillance in DLBCL. Specific functional studies are required to make an unambiguous link between genetic aberrations and biological impact on impaired immune surveillance.

KEYWORDS:

• Immune surveillance
• somatic mutation
• DLBCL
• candidate genes
• immune escape

Article highlights box

• Immune surveillance is a dynamic process composed of the innate and adaptive immune response that plays a crucial role in the identification and elimination of tumor cells

• The most frequently involved genes in immune surveillance are: CREBBP, TNFRSF14, B2M, HLA-B, CD70, HLA-A, EP300, CD58, CIITA, and FAS

• NGS technology is the main tool for mutational profiling

• The most popular platform in the reviewed studies was Illumina HiSeq 2000/2500

• Somatic mutations that are predictably damaging in genes related to immune surveillance are an important mediator of tumor escape from immune surveillance

• The comparison of paired diagnostic and relapse samples is a valuable tool for the determination of relapse specific genetic alterations

• Somatic mutations that have been predicted to be damaging prediction result in impaired expression of cell surface molecules in DLBCL, thus disabling immune-effector cells e.g. CTL and NK-cells

• Further evaluation of these mutations might lead to the creation of sequencing panels to detect immune surveillance loss.

Acknowledgments

Authors highly appreciate the professional help from librarian Conni Skrubbeltrang from the research library at Aalborg University Hospital.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was supported by the Heinrich Kopp’s Grant.