Investigating the diversity of malignant and immune cells in Head and Neck Cancer before and after immunotherapy

Immunotherapy has sparked a revolution in cancer treatment.  Unlike targeted therapies, immunotherapy can harness the patient’s own immune system to help target a cancer, offering a more flexible and durable form of treatment. Unfortunately, tumor responses to immunotherapy are highly variable across disease sites and among individual patients.

Head and neck squamous cell carcinoma is no exception: only 14-17% of patients respond to the therapy and there is no reliable way to identify who will have a positive response.  One reason the results vary so greatly is the complex mix of cell types in the tumor microenvironment.  Every tumor is made up of many different types of tumor cells all with different roles.  Immunotherapies may be rendered ineffective by certain mixes of cells or efficacy may rely on where in the tumor certain cells reside. Until now, scientists have not been able to characterize each individual cell in the tumor environment and see how it reacts to immunotherapy.

With his Cancer Research Foundation Young Investigator Award, Dr. Puram will use a new technique called single cell RNA-sequencing (scRNA-seq ) to characterize this heterogeneity in in head and neck small squamous cell carcinoma (HNSCC).  He has already been able to provide a glimpse of the diversity of cells in the tumor environment and using innovative imaging techniques he intends to list and categorize these cells and even map out where different types of cells are physically localized in the tumor microenvironment.  Dr. Puram will pursue this project using a matched set of tumor samples taken from HNSCC cancer patients both before and after they receive the immunotherapy.  By comparing these samples and being able to see which cells remain and where they are in relation to one another, both before and after treatment and in patients whose cancers are either receptive or unresponsive to the immunotherapy, Dr. Puram hopes to identify markers that can predict which patients should be given immunotherapy.  In the long run, this work may be able to uncover new ways clinicians could augment or better target immunotherapy so that it becomes far more effective for more patients.