IADR Abstract Archives
Characterizing Head and Neck Intra-Tumoral Heterogeneity for the Design of Patient-Specific Treatments
Objectives: Background: Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality, and its survival rate has not changed significantly over the past decades. Immunotherapy, which was recently incorporated as a treatment modality, has not substantially benefited most HNSCC patients. Heterogeneity in response to treatment, with varying response rates between tumor types, individuals, and various regions within the same tumor, constitutes a significant hurdle in the quest for predicting a successful outcome.
objectives: To characterize intra-tumoral heterogeneity by concurrently studying multiple aspects: (1) the patient-specific onco-protein expression levels. (2) The immune system, including the adaptive and innate immune systems. (3) The tumor microbiome.
Methods: Freshly resected oral squamous cell carcinoma (OSCC) tissues undergo: (1) Ex-vivo manipulation with experimental drugs and radiotherapy followed by flow-cytometry and computational single-cell analysis. (2) Implantation as patient-derived xenografts (PDX) in mice that are then treated in-vivo and analyzed as above. (3) Isolation and culturing of intra-tumoral bacteria. Paraffin-embedded tissues are analyzed for: (1) Components of the immune system using immunohistochemistry and a computerized quantification system. (2) Tumor intracellular microbiota using bacterial species-specific fluorescent in-situ hybridization (FISH). Finally, big-data biophysical methods are applied to identify correlations between all components.
Results: Distinct, patient-specific protein expression patterns and immune components were identified within the OSCC cohort of patients: (1) Correlation between radiotherapy and expression patterns of immune components. (2) Relation between anti-tumor and pro-cancer markers. (3) Differential expression of innate-immune system cells and ligands. (4) Intracellular microbiome within cancer cells.
Conclusions: By unveiling the relationship between multiple parameters comprising OSCC tumor environment, our next step is to identify factors that will allow us to predict response-to-treatment. We believe that this has the potential to revolutionize the treatment of OSCC toward personalized medicine and improved survival.
objectives: To characterize intra-tumoral heterogeneity by concurrently studying multiple aspects: (1) the patient-specific onco-protein expression levels. (2) The immune system, including the adaptive and innate immune systems. (3) The tumor microbiome.
Methods: Freshly resected oral squamous cell carcinoma (OSCC) tissues undergo: (1) Ex-vivo manipulation with experimental drugs and radiotherapy followed by flow-cytometry and computational single-cell analysis. (2) Implantation as patient-derived xenografts (PDX) in mice that are then treated in-vivo and analyzed as above. (3) Isolation and culturing of intra-tumoral bacteria. Paraffin-embedded tissues are analyzed for: (1) Components of the immune system using immunohistochemistry and a computerized quantification system. (2) Tumor intracellular microbiota using bacterial species-specific fluorescent in-situ hybridization (FISH). Finally, big-data biophysical methods are applied to identify correlations between all components.
Results: Distinct, patient-specific protein expression patterns and immune components were identified within the OSCC cohort of patients: (1) Correlation between radiotherapy and expression patterns of immune components. (2) Relation between anti-tumor and pro-cancer markers. (3) Differential expression of innate-immune system cells and ligands. (4) Intracellular microbiome within cancer cells.
Conclusions: By unveiling the relationship between multiple parameters comprising OSCC tumor environment, our next step is to identify factors that will allow us to predict response-to-treatment. We believe that this has the potential to revolutionize the treatment of OSCC toward personalized medicine and improved survival.