High TMB Fails to Show Predictive Biomarker Potential for Checkpoint Inhibition Across Cancers

High TMB Fails to Show Predictive Biomarker Potential for Checkpoint Inhibition Across Cancers

Publication date: May 23, 2021

The study evaluated over 10,000 patients across 31 cancer types who had available data in The Cancer Genome Atlas (TCGA). -While TMB status does show value in predicting response to immune checkpoint blockade in several cancer types, this was not generalizable across all cancers. The KEYNOTE-158 trial included patients with small cell lung cancer, cervical, endometrial, anal, vulvar, neuroendocrine, salivary, and thyroid cancers, as well as mesothelioma. In addition, the study found that the F1CDx assay overestimated TMB-H cancer-related genes compared with TMB from whole-exome sequencing data in 25 of 31 cancer types analyzed. Moreover, a negative correlation was observed between the median TMB in a given cancer type and the degree of TMB-H overestimation. As such, evaluating whether TMB-H could serve as a predictive biomarker in the latter subgroup was relevant to a large proportion of patients. Samples were categorized by whether CD8 T-cell infiltration positively correlated with neoantigen load.

Concepts Keywords
Biomarker Microsatellite instability
Cancer Checkpoint inhibitor
Cancers Pembrolizumab
Immunotherapy Tumor mutational burden
Melanoma Mutation
Prostate DNA
Thyroid Cancer immunotherapy
Immune system
Clinical medicine
Cancer treatments
Small lung cancer
Group cancers
Immunogenetic tumor
Status broader
TMB H cancer
Additional tumor


Type Source Name
disease MESH mesothelioma
disease MESH thyroid cancers
disease MESH small cell lung cancer
pathway KEGG Small cell lung cancer
pathway KEGG Colorectal cancer
drug DRUGBANK Irinotecan
drug DRUGBANK Oxaliplatin
disease MESH colorectal cancer
pathway KEGG Mismatch repair
drug DRUGBANK Pembrolizumab
pathway KEGG Glioma
disease MESH glioma
disease MESH bladder cancer
pathway KEGG Bladder cancer
disease MESH Cancers
disease MESH melanoma
pathway KEGG Melanoma

Original Article

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