Combined TCR Repertoire Profiles and Blood Cell Phenotypes Predict Melanoma Patient Response to Personalized
Asaf Poran1, Julian Scherer1, Meghan E Bushway1
1Neon Therapeutics/BioNTech US, Cambridge, MA, USA.
Abstract:
T cells use highly diverse receptors (TCRs) to identify tumor cells presenting neoantigens arising from genetic mutations and establish anti-tumor activity. Immunotherapy harnessing neoantigen-specific T cells to target tumors has emerged as a promising clinical approach. To assess whether a comprehensive peripheral mononuclear blood cell analysis predicts responses to a personalized neoantigen cancer vaccine combined with anti-PD-1 therapy, we characterize the TCR repertoires and T and B cell frequencies in 21 patients with metastatic melanoma who received this regimen. TCR-α/β-chain sequencing reveals that prolonged progression-free survival (PFS) is strongly associated with increased clonal baseline TCR repertoires and longitudinal repertoire stability. Furthermore, the frequencies of antigen-experienced T and B cells in the peripheral blood correlate with repertoire characteristics. Analysis of these baseline immune features enables prediction of PFS following treatment. This method offers a pragmatic clinical approach to assess patients' immune state and to direct therapeutic decision making.
Insights
Assessing T cell receptor repertoires and immune cell frequencies in peripheral blood can predict patient responses to personalized neoantigen cancer vaccines combined with anti-PD-1 therapy, aiding treatment decisions.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- T cells recognize tumor neoantigens via T cell receptors (TCRs) to mediate anti-tumor activity.
- Neoantigen-specific T cell-based immunotherapies are a promising strategy for cancer treatment.
- Predicting treatment response is crucial for optimizing personalized cancer vaccines and immunotherapies.
Purpose of the Study:
- To determine if peripheral blood immune cell analysis predicts response to personalized neoantigen cancer vaccine plus anti-PD-1 therapy.
- To characterize T cell receptor (TCR) repertoires and T and B cell frequencies in patients receiving this treatment.
Main Methods:
- TCR-α/β-chain sequencing was performed on peripheral blood samples from 21 metastatic melanoma patients.
- Analysis included baseline and longitudinal assessment of TCR repertoires and immune cell frequencies.
- Correlations between immune features and progression-free survival (PFS) were investigated.
Main Results:
- Increased clonal baseline TCR repertoires and longitudinal repertoire stability were strongly associated with prolonged PFS.
- Frequencies of antigen-experienced T and B cells correlated with TCR repertoire characteristics.
- Baseline immune profiles effectively predicted PFS in patients treated with neoantigen vaccine and anti-PD-1 therapy.
Conclusions:
- Peripheral blood immune cell analysis, including TCR repertoire assessment, can predict treatment response in metastatic melanoma.
- This approach offers a practical method for evaluating patient immune status and guiding therapeutic decisions.
- Immune profiling may enhance the efficacy of personalized cancer vaccines and combination immunotherapies.
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...