Dr. Dimou on Limitations of TMB as a Biomarker in Lung Cancer

Video

In Partnership With:

Anastasios (Tassos) Dimou, MD, discusses the limitations of tumor mutational burden as a biomarker in lung cancer.

Anastasios (Tassos) Dimou, MD, medical oncologist, Mayo Clinic, discusses the limitations of tumor mutational burden (TMB) as a biomarker in lung cancer.

High TMB has been shown to elicit greater response to immune checkpoint inhibitors in multiple tumor types, says Dimou. However, technical and biological limitations associated with TMB have limited its clinical utility as a biomarker in lung cancer.

Technical limitations include variations in targeted gene panel testing, preanalytical tissue fixation, and non-standardized cutoff points, explains Dimou.

Antigen presentation and the ability of the immune system to recognize and eliminate the mutated protein are biological considerations concerning TMB, says Dimou. Largely, these factors depend on human leukocyte antigen (HLA), which is often lost in patients with lung cancer.

Moreover, tumors that have loss of heterozygosity for the HLA result in defects in antigen presentation and therefore are not expected to respond to immune checkpoint inhibitors, concludes Dimou.

Related Videos
Shivaani Kummar, MBBS, FACP, Margaret and Lester DeArmond Endowed Chair of Cancer Research, Professor and Division Head, Division of Hematology/Medical Oncology, Oregon Health & Science University School of Medicine; co-director, Center for Experimental Therapeutics, co-deputy director, Knight Cancer Institute
Andre Goy, MD
Wenxin (Vincent) Xu, MD,
Guenther Koehne, MD, PhD
Alessandro Villa, DDS, PhD, MPH
Joseph Mikhael, MD
Michael Richardson, MD
Minesh Mehta, MD
Ruben Olivares, MD
Phillip J. Koo, MD