Related Experiment Video
Updated: Feb 24, 2026
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma
Alexandre Reuben1, Christine N Spencer2, Peter A Prieto1
1Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Abstract:
Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
Insights
Melanoma tumors show significant genomic and immune diversity, impacting how patients respond to targeted therapy and immune checkpoint blockade. Understanding this heterogeneity is key for personalized cancer treatment.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Genomic and immune heterogeneity are recognized in cancer, but their link to treatment response requires further study.
- Melanoma exhibits significant variability, complicating treatment strategies.
Purpose of the Study:
- To investigate the relationship between genomic and immune heterogeneity and treatment response in melanoma patients.
- To identify factors influencing differential responses to targeted therapy and immune checkpoint blockade.
Main Methods:
- Analysis of a cohort of 60 melanoma patients receiving targeted therapy or immune checkpoint blockade.
- Deep genomic and immune profiling of synchronous melanoma metastases.
- Radiologic and radiomic assessment of therapeutic responses.
Main Results:
- Observed heterogeneity in therapeutic responses across the majority of patients.
- Demonstrated substantial genomic and immune heterogeneity within individual patients.
- Identified significant diversity in T cell frequency and limited shared T cell clones across the cohort.
Conclusions:
- Melanoma exhibits extensive intratumoral heterogeneity impacting treatment outcomes.
- Genomic and immune profiling, alongside radiomics, can identify predictors of response.
- Findings have significant translational implications for precision medicine in melanoma.
Related Concept Videos
01:27Tumor Immunotherapy
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...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:22Diversity in Cell Signaling Responses
Graded and Abrupt Responses
Some signaling systems generate...