Key Points
• In the current study, researchers assessed tumor mutational burden (TMB) and immune phenotype in 223 lung adenocarcinoma (LUAD) patients to elucidate potential mechanisms for poor efficacy of immune checkpoint blockades (ICBs) in EGFR-positive mutated patients. They also sought other factors that could impact the tumor immune phenotype to suggest new drug targets and combination therapies.
• They found that the median TMB level was mutations/Mb, with this level related to age, gender, and EGFR mutation status. Fewer EGFR-mutant patients exhibited mutated KRAS and BRCA2. The investigators also discovered that patients with or without metastatic lesions exhibited different immune phenotype, with the mutational frequencies of ALK, CDKN2A, MAP2K1, IDH2 and PTEN varying among three immune phenotypes.
• “As TMB alone may not be a perfect predictor and cancer cells have complex interactions with immune cells, tumor immune microenvironment should also be considered as an impact factor for immune therapy,” the authors wrote. “TMB could reflect the neoantigen burden of the tumor indirectly and neoantigen partially reflected the tumor immunogenicity which also played a significant role in determining tumor immune microenvironment.”
• Limitations of the current study included a smaller sample size. The researchers also employed targeted panel sequencing to analyze the TMB, consequently mutations in genes that are not a part of the panel were not identified or analyzed. Another limitation was that the researchers did not utilize multi-site samples to evaluate the TMB, thus the potential influence of heterogeneity of tumor TMB could not be defined.
• “Low TMB level could be the reason for the poor efficacy of ICBs in patients having EGFR mutation,” the authors concluded. “And mutational frequencies of KRAS and BRCA2 were lower in EGFR-mutant patients. Furthermore, ALK, CDKN2A, MAP2K1, IDH2 and PTEN might involve in the formation of immune phenotypes.”