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TMB: a promising immune-response biomarker, and potential spearhead in advancing targeted therapy trials
Khalil Choucair1, Susan Morand2, Laura Stanbery2
1Department of Internal Medicine, University of Kansas School of Medicine, Wichita, KS, USA.
Abstract:
Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, we review checkpoint inhibitor signal pathways, resistance and sensitivity mechanisms, as well as response rates. We also investigate the correlation and response to ICI with BRCA1/2 mutation status and homologous recombination deficient tumors. Collectively we show that the use of tumor mutational burden may be effective as an emerging biomarker.
Insights
Immune checkpoint inhibitors (ICI) offer durable cancer treatment responses. However, identifying non-responders, even with PD-L1 expression, necessitates new biomarkers like tumor mutational burden for improved cancer therapy effectiveness.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immune checkpoint inhibition (ICI) has transformed cancer therapy, yielding durable responses in numerous cancer types.
- A significant subset of patients do not respond to ICI, even with PD-L1 expression, indicating a need for superior biomarkers.
- Understanding resistance and sensitivity mechanisms is crucial for optimizing ICI efficacy.
Purpose of the Study:
- To review ICI signal pathways, resistance/sensitivity mechanisms, and response rates.
- To investigate the correlation between ICI response and BRCA1/2 mutation status.
- To explore the role of homologous recombination deficiency (HRD) in ICI response.
Main Methods:
- Literature review of immune checkpoint inhibitor pathways.
- Analysis of existing data on ICI response rates.
- Investigation of correlations between ICI efficacy, BRCA1/2 mutations, and HRD status.
Main Results:
- Review of established ICI mechanisms and clinical outcomes.
- Exploration of BRCA1/2 mutation status and HRD as potential predictive markers for ICI.
- Identification of tumor mutational burden (TMB) as a promising emerging biomarker for ICI response.
Conclusions:
- Tumor mutational burden shows potential as an effective biomarker for predicting response to immune checkpoint inhibitors.
- Further research into TMB and other biomarkers is essential to improve patient selection for ICI therapy.
- Integrating multiple biomarkers may enhance the precision of cancer treatment strategies.
